Primary Outcomes

Description: Survival estimates will include death from any cause.

Measure: Overall Survival

Time: From date of randomization through study completion, up to 10 years

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Secondary Outcomes

Description: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Lung Cancer (LC 13) survey instruments will assess patients' general state of physical, social/family, emotional and functional well-being.

Measure: Patient reported health-related quality of life

Time: 5 years

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Description: The St George's Respiratory Questionnaire will evaluate respiratory symptoms, activity limitations from breathlessness, and impact of respiratory function on social and psychological functioning.

Measure: Respiratory Symptoms

Time: 5 years

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Description: The EQ-5D-5L (EuroQOL-5D) survey will measure quality adjusted life years.

Measure: Health State Utilities

Time: 5 years

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Description: Cause of death will be determined by an independent adjudication committee.

Measure: Lung cancer mortality

Time: From date of randomization until date of death from any cause, assessed up to 10 years.

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Description: Post-treatment surveillance imaging will evaluate patients every 6 months for local, regional, and/or distant disease control.

Measure: Tumor patterns of failure

Time: 5 years

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Description: The Forced Expiratory Volume at 1 second (FEV1) will evaluate an objective measure of breathing function.

Measure: Respiratory Function

Time: 5 years

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Primary Outcomes

Description: Complete Response (CR) Disappearance or fibrosis of all target lesions. Any pathologic lymph nodes must have reduction in short axis to <10mm and standardized uptake value (SUV) is <4. Partial Response (PR) At least 30% decrease in sum of longest diameters of target lesions (compared to initial on study baseline) and any decrease in SUV in Fludeoxyglucose 18F (18FDG) imaging Stable disease (SD) 0-29% decrease in sum of longest diameters of target lesions (compared to initial on study baseline) or 0-19% increase in sum of longest diameters of target lesions (compared to initial on study baseline). SUV may increase or decrease Progressive disease 20% or more increase of sum of longest diameters of target lesions (compared to initial on study baseline). The sum must also be at an increase of at least 5mm or one or more new lesions that are considered metastatic disease

Measure: Tumor response according to RECIST Criteria

Time: Up to 1 Year

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Secondary Outcomes

Description: Average time from beginning of treatment to progression, death, or one year, whichever comes first. An underlying clinical benefit rate of 25% would indicate that ONC201 has a therapeutic effect, whereas an underlying rate <5% would indicate a lack of activity

Measure: Average duration of lack of progression: Clinical response

Time: Up to 1 Year

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Description: time from beginning of treatment until death, or one year, whichever comes first.

Measure: Overall survival

Time: Up to 1 Year

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Description: to achieve this secondary endpoint of anti-hypertensive medication reduction in PC-PG subjects (N=12) data at 3 months will be required. An underlying clinical benefit rate of 25% would indicate that ONC201 has a therapeutic effect, whereas an underlying rate <5% would indicate a lack of activity

Measure: Average change in anti-hypertensive medication

Time: from beginning of treatment to 3 months

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Primary Outcomes

Description: DLT as graded using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 4.03. The DLT observation period may be increased if deemed appropriate by the Dose Escalation and Safety Committee

Measure: Safety and tolerability assessed by Dose Limiting Toxicity (DLT)

Time: Up to 21 days

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Description: Initial and re-treatment. An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product

Measure: Safety and tolerability assessed by adverse events (AEs)

Time: Up to 30 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 52 weeks)

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Description: Initial and re-treatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies

Measure: Safety and tolerability assessed by immune-related AEs (irAEs)

Time: Up to 30 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 52 weeks)

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Description: Initial and re-treatment. Adverse event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event

Measure: Safety and tolerability assessed by serious adverse events (SAEs)

Time: Up to 90 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 60 weeks)

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Description: Initial and re-treatment. Number of participants with potentially clinically significant laboratory values. The laboratory tests include hematology, biochemistry, urine dipstick, pregnancy test, thyroid stimulating hormone (TSH) and free T4; Hepatitis B and C; Testosterone and prostate-specific antigen (PSA) (metastatic castration resistant prostate cancer (mCRPC) only)

Measure: Number of participants with laboratory value abnormalities and/or adverse events related to treatment

Time: Up to 30 days from last dose in safety follow up period for each treatment period (Up to a maximum of 52 weeks)

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Description: Initial and re-treatment. ECGs should be obtained after the participant has rested quietly and is awake in a fully supine position (or semi-recumbent, if supine is not tolerated) for 10 minutes before the first ECG from a triplicate or single ECG. Any clinically significant adverse changes on the ECG will be reported as (serious) Adverse Event

Measure: Safety and tolerability assessed by 12-lead electrocardiogram (ECG)

Time: Up to end of treatment (up to 48 weeks for each treatment period)

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Description: Initial and re-treatment. Number of participants with potentially clinically significant vital sign values. Vital signs will include systolic and diastolic blood pressure, radial pulse and temperature. All vital signs will be measured with the subject in the sitting or supine position

Measure: Number of participants with vital signs abnormalities and/or adverse events related to treatment

Time: Up to 90 days from last dose in safety follow up period for each treatment period (Up to a maximum of 60 weeks)

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Description: Initial and re-treatment. Standard, full physical examinations will be performed at screening to assess general appearance, skin, eyes, ears, nose, throat, neck, cardiovascular system, chest and lungs, abdomen, musculoskeletal system, neurologic status, mental status, and lymphatic system

Measure: Number of participants with Physical Exam abnormalities and/or adverse events related to treatment

Time: Up to end of treatment (up to 48 weeks for each treatment period)

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Description: Initial and re-treatment. The eastern cooperative oncology group (ECOG) Scale [Oken, 1982] will be used to assess performance status.0 = Fully active, able to carry on all predisease performance without restriction; 1=Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature; 2= Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3= Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4= Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

Measure: Safety and tolerability assessed by ECOG performance status

Time: Up to 30 days from last dose in safety follow up period of each treatment period (Up to a maximum of 52 weeks)

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Description: AUClast: area under the concentration-time curve from the time of dosing to the last measurable concentration. AUClast will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: AUClast (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only)

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Description: AUCinf: area under the concentration-time curve from the time of dosing extrapolated to time infinity. AUCinf will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: AUCinf (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 1: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only)

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Description: AUCtau: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval. AUCtau will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: AUCtau (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only)

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Description: Cmax: maximum concentration. Cmax will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: Cmax (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only)

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Description: Ctrough: Trough concentration. Ctrough will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: Ctrough (Initial treatment, escalation and expansion cohorts in both monotherapy and combination therapy)

Time: Cycle 2, 4, 7, 10 and 15: day 1: predose 0 hr

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Description: Ctrough: Trough concentration. Ctrough will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of pembrolizumab in serum: Ctrough (Initial treatment, escalation cohorts in combination therapy)

Time: Cycle 2, 4, 7, 10 and 15: day 1: predose 0 hr

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Description: Ctrough: Trough concentration. Ctrough will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: Ctrough (Re-treatment, escalation and expansion cohorts in both monotherapy and combination therapy)

Time: Cycle 5, 10 and 15: day 1: predose 0 hr

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Description: tmax: time of maximum concentration. tmax will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: tmax (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only)

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Description: t1/2: terminal elimination half-life. t1/2 will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: t1/2 (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 1: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose

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Description: CL: Clearance. CL will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: CL (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only)

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Description: Vz: Volume of distribution after intravenous dosing during the terminal elimination phase. Vz will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: Vz (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 1: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose

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Description: Vss: Volume of distribution at steady state after intravenous dosing. Vss will be derived from the PK serum samples collected.

Measure: Pharmacokinetics (PK) of ASP8374 in serum: Vss (Initial treatment, escalation cohorts in monotherapy only)

Time: Cycle 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose

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Secondary Outcomes

Description: Initial and re-treatment. 'Immune' Response Evaluation Criteria in Solid Tumors (iRECIST). ORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR or PR

Measure: Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST

Time: Up to end of follow up period (up to 105 weeks) of each treatment period

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Description: Initial and re-treatment. DOR will be calculated only for the subgroup of participants with confirmed response CR/PR

Measure: Duration of response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST

Time: Up to end of follow up period (up to 105 weeks) of each treatment period

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Description: Initial and re-treatment. Persistence of response after discontinuation is defined for participants who discontinued the treatment and responded to the treatment per iRECIST only

Measure: Persistence of response after discontinuation by iRECIST

Time: Up to end of follow up period (up to 105 weeks) of each treatment period

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Description: Initial and re-treatment. DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or Stable Disease (SD)

Measure: Disease control rate (DCR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST

Time: Up to End of follow up period (up to 105 weeks) of each treatment period

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Primary Outcomes

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)

Time: Up to 36 months

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Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With Dose Limiting Toxicities (DLTs)

Time: Up to 36 months

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Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With one or More Serious Adverse Events (SAEs)

Time: Up to 36 months

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Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With one or More TEAEs Leading to Dose Modifications and Treatment Discontinuations

Time: Up to 36 months

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Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With Greater Than or Equal to (>=) Grade 3 TEAEs

Time: Up to 36 months

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Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With Clinically Significant Laboratory Values

Time: Up to 36 months

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Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants With Clinically Significant Vital Sign Measurements

Time: Up to 36 months

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Description: CRS will be graded as per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.

Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants who Experience Cytokine Release Syndrome CRS)

Time: Up to 36 months

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Measure: COVID-19 Expansion: Number of Participants With >=2 log Reduction From Baseline in Viral Load or Below Level of Detection (Negative) in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

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Secondary Outcomes

Measure: Dose Escalation and Cancer Treatment Expansions, Cmax: Maximum Observed Plasma Concentration for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length is equal to [=] 21 days)

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Measure: Dose Escalation and Cancer Treatment Expansions, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Dose Escalation and Cancer Treatment Expansions, AUCt: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Dose Escalation and Cancer Treatment Expansions, AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Dose Escalation and Cancer Treatment Expansions, Terminal Disposition Phase Half-life (t1/2z) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Dose Escalation and Cancer Treatment Expansions, Total Clearance After Intravenous Administration (CL) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Measure: Dose Escalation and Cancer Treatment Expansions, Volume of Distribution at Steady State After Intravenous Administration (Vss) for TAK-981

Time: Cycle 1 Day 1 pre-dose and at multiple time points (up to 48 hours) post dose; Cycle 1 Day 8 pre-dose and at multiple time points (up to 24 hours) post dose (Cycle length =21 days)

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Description: ORR is defined as percentage of participants who achieve complete response (CR) and partial response (PR) through the study (approximately 3 years), as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for participants with solid tumors and Response Evaluation Criteria in Lymphoma (RECIL) for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Overall Response Rate (ORR)

Time: From the first dose until best response is achieved (up to approximately 3 years)

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Description: DOR will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Duration of Response (DOR)

Time: From the time of documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study (up to approximately 3 years)

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Description: DCR is defined as percentage of participants who achieve stable disease (SD) or better greater than (>) 6 weeks during the study in response-evaluable population, as determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Disease Control Rate (DCR)

Time: From the first dose until best response is achieved (up to approximately 3 years)

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Description: PFS will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Progression-free Survival (PFS)

Time: From the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study (up to approximately 3 years)

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Description: TTR will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.

Measure: Dose Escalation and Cancer Treatment Expansions: Time to Response (TTR)

Time: From the date of first study drug administration to the date of first documented PR or better (up to approximately 3 years)

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Measure: Dose Escalation and Cancer Treatment Expansions: Percentage of Participants at Each Dose Level Demonstrating Adduct Formation in Post-dose Skin or Tumor Biopsies

Time: Up to Cycle 1 (approximately 3 weeks) (Cycle length =21 days)

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Measure: Dose Escalation and Cancer Treatment Expansions: Percent Change in Small Ubiquitin-like Modifier (SUMO) 2/3 Signal With Pre and Post-dose Skin or Tumor Biopsies at Each Dose Level

Time: Up to Cycle 1 (approximately 3 weeks) (Cycle length =21 days)

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Measure: COVID-19 Expansion: Number of Participants Reporting one or More TEAEs

Time: Up to 9 months

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Description: Severity Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 5.0.

Measure: COVID-19 Expansion: Number of Participants Based on Severity of TEAEs

Time: Up to 9 months

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Measure: COVID-19 Expansion: Number of Participants Based on Duration of TEAEs

Time: Up to 9 months

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Description: CRS will be graded as per ASTCT Consensus Grading for CRS.

Measure: COVID-19 Expansion: Number of Participants who Experience CRS

Time: Up to 9 months

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Description: NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.

Measure: COVID-19 Expansion: Change from Baseline in National Early Warning Score (NEWS)

Time: Up to 9 months

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Description: Percentage of participants will be reported based on severity rating on a 6-point ordinal scale, which will include: 1 (death); 2 (hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation, hospitalized); 3 (on non-invasive ventilation or high flow oxygen devices); 4 (hospitalized, requiring supplemental oxygen); 5 (hospitalized, not requiring supplemental oxygen); and 6 (not hospitalized).

Measure: COVID-19 Expansion: Percentage of Participants Reporting Each Hospitalization Severity Rating

Time: Up to 9 months

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Description: Change from Baseline in SARS-CoV-2 viral Load in nasopharyngeal or oropharyngeal samples will be determined by viral response. The nasopharyngeal swab will be collected from both nostrils or from the same nostril every time.

Measure: COVID-19 Expansion: Change From Baseline in SARS-CoV-2 Viral Load in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

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Measure: COVID-19 Expansion: Percentage of Participants Requiring Oxygen Supplementation; Assisted or Positive Pressure Non-invasive Ventilation; and Invasive Ventilation, on Days 3, 5, 8, 11, 15, and 30

Time: Days 3, 5, 8, 11, 15, and 30

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Measure: COVID-19 Expansion: Percentage of Participants That met Intensive Care Unit (ICU) Criteria

Time: Up to 9 months

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Measure: COVID-19 Expansion: Duration of Hospitalization

Time: Up to 9 months

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Description: Time from the first dose of TAK-981 to viral load negativity (below level of detection).

Measure: COVID-19 Expansion: Time to Viral Ribonucleic Acid (RNA) Negativity in Nasopharyngeal or Oropharyngeal Samples

Time: Up to 9 months

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Description: Time from first dose of TAK-981 to participant's discharge or to NEWS score <=3. NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.

Measure: COVID-19 Expansion: Time to Discharge or to a NEWS of Less Than or Equal to (<=) 3 and Maintained for 24 Hours

Time: Up to 9 months

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Measure: COVID-19 Expansion: Number of Deaths in Hospital due to any Cause in First 30 Days and in 90 Days

Time: Days 30 and 90

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Primary Outcomes

Description: Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.

Measure: Incidence of Adverse Events of MGC018 and MGC018 + MGA012 as assessed by CTCAE v4.03

Time: 30 days after last dose

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Description: Maximum tolerated or maximum administered dose of MGC018 and MGC018 + MGA012

Measure: Maximum Tolerated Dose

Time: up to 42 days from first dose

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Secondary Outcomes

Description: Efficacy assessed as best overall response rate using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

Measure: Preliminary anti-tumor activity of MGC018 and MGC018+MGA012

Time: 24 months

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Description: Percent of prostate cancer patients with at least 50% reduction in prostate-specific antigen (PSA)

Measure: PSA response rate

Time: 24 months

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Description: For prostate cancer patients, time from first dose to first radiographic progression in soft tissue or bone, or death from any cause

Measure: Radiographic progression-free survival

Time: 24 months

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Description: For prostate cancer patients, change from baseline in pain intensity as measured by the Brief Pain Inventory-Short Form scale

Measure: Patient-reported Outcome

Time: 24 months

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Description: Area under the plasma concentration versus time curve of MGC018 and MGC018+MGA012

Measure: Area under the curve

Time: 24 months

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Description: Maximum Plasma Concentration of MGC018 and MGC018+MGA012

Measure: Cmax

Time: 24 months

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Description: Time to reach maximum (peak) plasma concentration of MGC018 and MGC018+MGA012

Measure: Tmax

Time: 24 months

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Description: Trough plasma concentration of MGC018 and MGC018+MGA012

Measure: Ctrough

Time: 24 months

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Description: Total body clearance of the drug from plasma of MGC018 and MGC018+MGA012

Measure: CL

Time: 24 months

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Description: Apparent volume of distribution at steady state of MGC018 and MGC018+MGA012

Measure: Vss

Time: 24 months

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Description: Terminal half life of MGC018 and MGC018+MGA012

Measure: t1/2

Time: 24 months

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Description: Percent of patients with anti-drug antibodies against MGC018 and MGA012

Measure: Immunogenicity

Time: 24 months

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Primary Outcomes

Description: DLTs will be evaluated during the first cycle. The number of DLTs will be used to determine the maximum tolerated dose (MTD)

Measure: Number of participants with dose limiting toxicities (DLTs)

Time: Baseline through day 28

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Description: Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy

Measure: Number of participants with treatment emergent adverse events (AEs)

Time: Baseline through up to 2 years or until disease progression

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Description: Laboratory abnormalities as characterized by type, frequency, severity, and timing.

Measure: Number of participants with laboratory abnormalities

Time: Baseline through up to 2 years or until disease progression

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Description: Best Overall Response by RECIST 1.1

Measure: Objective Response Rate

Time: Baseline through up to 2 years or until disease progression

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Secondary Outcomes

Description: Single dose PK will be calculated including Maximum Observed Plasma Concentration (Cmax).

Measure: Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including Time to reach Maximum Observed Plasma Concentration (Tmax).

Measure: Pharmacokinetic Parameters: Time to reach Maximum Observed Plasma Concentration (Tmax)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast)

Measure: Pharmacokinetic Parameters: Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including, as data permit, terminal elimination half life (t1/2)

Measure: Pharmacokinetic Parameters: Terminal elimination half life (t1/2)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including, as data permit, Area Under the Curve from time 0 extrapolated to infinity (AUCinf)

Measure: Pharmacokinetic Parameters: AUC from time 0 extrapolated to infinity (AUCinf)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including, as data permit, apparent oral plasma clearance (CL/F)

Measure: Pharmacokinetic Parameters: Apparent oral plasma clearance (CL/F)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Single dose PK will be calculated including, as data permit, apparent volume of distribution (Vz/F)

Measure: Pharmacokinetic Parameters: Apparent volume of distribution (Vz/F)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including Maximum Observed Steady State Plasma Concentration (Css,max).

Measure: Pharmacokinetic Parameters: Maximum Observed Steady State Plasma Concentration (Css,max)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max).

Measure: Pharmacokinetic Parameters: Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including Area Under the Curve within one dose interval (AUCss,t)

Measure: Pharmacokinetic Parameters: Area Under the Curve within one dose interval (AUCss,t)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including, as data permit, steady state apparent oral plasma clearance (CL/F)

Measure: Pharmacokinetic Parameters: Steady state apparent oral plasma clearance (CL/F)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8. 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including, as data permit, steady state apparent volume of distribution (Vss/F)

Measure: Pharmacokinetic Parameters: Steady state apparent volume of distribution (Vss/F)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: Multiple dose PK will be calculated including, as data permit, accumulation ratio (Rac)

Measure: Pharmacokinetic Parameters: Accumulation ratio (Rac)

Time: Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24

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Description: DOR as assessed using RECIST 1.1

Measure: Duration of response (DOR)

Time: Baseline through up to 2 years or until disease progression

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Description: PFS as assessed using RECIST 1.1.

Measure: Progression free survival (PFS)

Time: Baseline through up to 2 years or until disease progression

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Description: TTP as assessed using RECIST 1.1.

Measure: Time to progression (TTP)

Time: Baseline through up to 2 years or until disease progression

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Description: Proportion of participants alive at 6 months, 1 year and 2 years.

Measure: Overall Survival (OS)

Time: Baseline through up to 2 years

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Primary Outcomes

Description: FACIT Spiritual Well-Being Scale is a brief self-report measure designed to assess the nature and extent of individual spiritual well-being. This measure, which generates two sub-scales, one corresponding to Faith (the importance of faith and spirituality) and a second assessing Meaning-Peace (one sense of meaning and purpose in life), has been demonstrated to have strong internal reliability for both the total score as well as each subscale (coefficient alpha equals .87 for the total scale, .88 for the faith factor and .81 for the meaning factor). In additional, strong support for the external validity of this measure has been demonstrated in a several large samples of cancer and AIDS patients and with Spanish speaking populations.

Measure: Spiritual Well-Being measured with the FACIT Spiritual Well-Being Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Secondary Outcomes

Description: The Hospital Anxiety and Depression Scale (HADS) is a validated scale used to measure anxiety and depression. This scale has been validated against structured or semi-structured clinical interviews, the gold standard for the assessment of mental disorders, in a significant number of studies. Further strengths of this scale for the assessment of emotional distress in cancer patients stem from the joint assessment of anxiety and depressive symptoms without referring to physical symptoms of anxiety or depression. Given the high comorbidity of anxiety of cancer as well as the systematic exclusion of confounding physical symptoms, the scale seems especially appropriate for use in this patient group. The HADS consists of 14 items which reflect a 7-item anxiety and a 7-item depression subscale. This scale has sound psychometric properties in Spanish.

Measure: Depression and Anxiety measured with the Hospital Anxiety and Depression Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Description: The Beck Hopelessness Scale (BHS) comprises 20 true/false questions that assess degree of pessimism and hopelessness. Several studies have demonstrated a high degree of internal consistency and construct validity. Scores ranging from 4 to 8 typically indicate a "mild" degree of hopelessness, 9 to 12 correspond to "moderate" hopelessness, and scores about 12 reflect "severe" levels of hopelessness.

Measure: Hopelessness measured with the Beck Hopelessness Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Description: The FACIT Spiritual Well-Being Scale (FACIT-Sp-12) is a brief self-report measure designed to assess the nature and extent of individual's spiritual well-being. This measure (range 0-48), which generates two sub-scales, Faith (the importance of faith/spirituality, range 0-16) and Meaning /Peace (one's sense of meaning and purpose in life, range 0-32). The total score for the FACIT-Sp scale is the sum of the two subscales Faith and Meaning /Peace. It has been demonstrated to have strong internal reliability for both the total score as well as each subscale (coefficient alpha = .87 for the total scale, .88 for the faith factor and .81 for the meaning factor). Higher scores represent a higher level of spiritual well-being, faith or meaning-peace. In addition, strong support for the external validity of this measure has been demonstrated in a several large samples of cancer and AIDS patients and with Spanish speaking populations. Administration time takes approximately 4 minutes.

Measure: Quality of life measured with the FACIT Spiritual Well-Being Scale

Time: Change from baseline to post assessment 7-14 weeks after

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Primary Outcomes

Description: The primary outcome is the proportion of patients who have a goals-of-care (GOC) discussion that has been documented in the EHR in the period between randomization and 30 days following randomization The proportion is the number of patients with GOC documentation over the number of patients in each study arm. Documentation of goals-of-care discussions will be evaluated using our NLP/ML methods. Study staff will manually review and compare findings using a randomly-selected sample of charts using our standard EHR abstraction methods; manual chart abstraction will be the gold standard.

Measure: EHR documentation of Goals of Care discussions

Time: Assessed for the period between randomization and 30 days following randomization

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Secondary Outcomes

Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of ICU admissions during the patient's (index) hospital stay will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care/ICU use: ICU admissions

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of days the patient spent in the ICU during their (index) hospital stay will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care/ICU use: ICU length of stay

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of days the patient spent in the hospital during that (index) hospital stay will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care/Hospital use: Hospital length of stay

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of hospital readmissions between randomization and 30 days following randomization will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care: Hospital Readmissions 30 days

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Secondary outcomes include measures of intensity of care, including utilization metrics: Number of ICU readmissions between randomization and 30 days following randomization will be collected from the EHR using our automated and validated methods.

Measure: Intensity of care: ICU Readmissions 30 days

Time: Assessed for the period between randomization and 30 days following randomization

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Description: Costs for intervention vs. control will be reported in US dollars and identified from UW Medicine administrative financial databases. Costs will be reported for total hospital costs and disaggregated costs (direct-variable, direct fixed, indirect costs). Direct-variable costs will include supply and drug costs. Direct-fixed costs will include labor, clinical department administration, and overhead fees. Indirect costs represent services provided by cost centers not directly linked to patient care such as information technology and environmental services. Costs for ED (emergency department) days and ICU days will be similarly assessed.

Measure: Intensity of care: Healthcare costs

Time: 1 and 3 months after randomization

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Description: From Washington State death certificates.

Measure: All-cause mortality at 1 year (safety outcome)

Time: 1 year after randomization

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Other Outcomes

Description: Qualitative interviews after individual participation. Interviews will be guided by the RE-AIM and Consolidated Framework for Implementation Research (CFIR) to explore the factors associated with implementation (e.g., reach, maintenance, feasibility, inner and outer settings, individuals, and processes of care.) Individual constructs within these domains were chosen to fit this specific intervention and context.

Measure: Key Implementation Factors

Time: 3 months after randomization

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Primary Outcomes

Description: Incidence rate of SARS-CoV-2 infection within the whole period of the study.

Measure: SARS-CoV-2 infection

Time: through study completion, an average of 3 months.

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Secondary Outcomes

Description: Tumor response by determining changes (PD, SD, PR, CR) according to Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1

Measure: Tumor response

Time: 6 weeks after enrollment.

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Description: Safety and tolerability of chemotherapy as measured by the Common Terminology Criteria for Adverse Events (version 4.0)

Measure: Safety and tolerability

Time: through study completion, an average of 3 months.

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Description: Patient-reported outcomes are measured using the EORTC quality of life questionnaire core-30 (QLQ-C30).

Measure: Patient-reported outcomes

Time: through study completion, an average of 3 months.

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Primary Outcomes

Description: modification of the planned therapeutic management

Measure: percentage of patients with a change in the planned therapeutic management (surgery, chemotherapy, radiotherapy, hormone therapy)

Time: Day O

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Primary Outcomes

Description: The percentage of HM patients with COVID-19 who died.

Measure: To evaluate mortality.

Time: At 2 months from study initiation

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Description: We will assess the correlation between some biochemical parameters at diagnosis of COVID (i.e. hemoglobin, platelets, lymphocytes, clotting tests, CRP), each on the basis of its specific unit of measure, and mortality.

Measure: To evaluate potential predictive biochemical parameters of mortality.

Time: At 2 months from study initiation

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Description: We will assess the correlation between HM-related parameters at diagnosis of COVID [i.e. disease type (leukemia, lymphomas, myeloma), disease status (remission / stable / progression), therapy status (on / off therapy)] and mortality.

Measure: To evaluate potential predictive HM-related parameters of mortality.

Time: At 2 months from study initiation

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Description: We will assess the correlation between COVID severity [mild (non-pneumonia and mild pneumonia), severe (dyspnea, respiratory frequency ≥ 30/min, SpO2 ≤ 93%, PaO2/FiO2 < 300 and/or lung infiltrates > 50%) and critical (respiratory failure, septic shock, and/or multiple organ disfunction or failure)] and mortality

Measure: To evaluate COVID severity as predictive parameter of mortality.

Time: At 2 months from study initiation

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Secondary Outcomes

Description: Description of the different types of hematological malignancies (WHO criteria) in patients with SARS-CoV-2 infection. All aggregated data will be stratified on the basis of COVID severity: mild (non-pneumonia and mild pneumonia), severe (dyspnea, respiratory frequency ≥ 30/min, SpO2 ≤ 93%, PaO2/FiO2 < 300 and/or lung infiltrates > 50%) and critical disease (respiratory failure, septic shock, and/or multiple organ disfunction or failure)

Measure: Epidemiology of patients with HM infected by SARS-CoV-2with any spectrum of illness severity

Time: At 6 months from study initiation

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Description: Characterization of clinical and biochemical profile of patients with SARS-CoV-2 positivity.

Measure: Definition of complete clinical picture of COVID-19 in HM

Time: At 2 months from study initiation

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Description: Assessment of HM status post SARS-CoV-2 infection stratified as no implication, loss of response, progression of the hematological disease.

Measure: Evolution of HM

Time: At 2 months from study initiation

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Description: Percentage of HM patients being admitted to ICU requiring mechanical ventilation, or death stratified per disease type, status, per off-therapy/on-therapy, per type of therapy (chemo, immunotherapy, cell therapy, stem cell transplant).

Measure: To evaluate admission to ICU requiring mechanical ventilation or death per characteristics

Time: At 2 months from study initiation

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Measure: Viral dynamics in infected HM patients

Time: At 12 months from study initiation

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Primary Outcomes

Description: The survey includes five parts: 1) basic demographics about the patient, including performance status and comorbidities; 2) initial COVID-19 diagnosis and clinical course; 3) cancer and cancer treatment details; 4) respondent details; 5) long-term COVID-19 outcomes.

Measure: Web-based REDCap survey

Time: Approximately 18 months

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Primary Outcomes

Description: The 7-day length of invasive MV for each arm will be estimated with 95% confidence intervals (CIs) using the exact binomial distribution. Their difference by the arms will be tested by Cochran-Mantel-Haenszel (CMH) test stratified by the age group and Sequential Organ Failure Assessment (SOFA) score at significance level of 0.05.

Measure: 7-day length of invasive mechanical ventilation (MV)

Time: Up to 7 days

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Description: Defined as death within 30-day after randomization. The 30-day mortality rate for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

Measure: 30-day mortality rate

Time: Up to 30-day after randomization

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Secondary Outcomes

Description: The rate of ICU transfer for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

Measure: Rate of intensive care (ICU) transfer

Time: Up to 2 years

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Description: The rate of invasive mechanical ventilation for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

Measure: Rate of invasive mechanical ventilation

Time: Up to 2 years

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Description: The rate of tracheostomy for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.

Measure: Rate of tracheostomy

Time: Up to 2 years

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Description: Will first be described by median and inter-quartile, and then compared between two arms by Wilcoxon Sum-Rank test

Measure: Length of ICU stay

Time: Up to 2 years

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Measure: Length of hospital stay

Time: Up 2 years

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Primary Outcomes

Description: The primary endpoint of this study is the recurrence of COVID-19 within 3 months following the immunoassay-positive result obtained before the inclusion in the study. The recurrence is defined by the presence of symptoms confirmed either by a positive reverse transcription-polymerase chain reaction (RT-PCR) result for SARS-CoV-2 or by the adjudication committee. Immunoassay will be said positive as per the predefined reference corresponding to the immunoassay.

Measure: To evaluate the ability of SARS-CoV-2 immunoassays, following a positive result, to identify patients with very low risk of recurrence of COVID-19 within 3 months.

Time: 3 months

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Secondary Outcomes

Description: The prevalence is the ratio between the number of immunoassay-positive patients and the number of patients tested over a predefined period, i.e the whole duration of the study and by 1-month intervals.

Measure: To estimate the prevalence of patients immunized to the SARS-CoV-2 virus in an oncology population over the whole study duration and within one-month periods.

Time: 6 months

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Description: Agreement between the different immunoassays and the centralized ELISA, using the centralized ELISA as benchmark.

Measure: To estimate the discordance rate between local immunoassay and a centralized ELISA in patients with a positive immunoassay, whatever the immunoassay.

Time: 6 months

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Description: COVID-19 recurrence within 6 months following an immunoassay-positive result.

Measure: To identify patients with very low risk of recurrence of COVID-19 within 6 months following a positive immunoassay result.

Time: 6 months

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Description: Quantitative and qualitative detection of SARS-CoV-2-related antibodies and immune serum markers at baseline, 2-3 months and 4-6 months post-inclusion, in a subgroup of 200 patients.

Measure: To characterize the evolution over time of the serologic response against SARS-CoV-2 (in a subgroup of patients).

Time: 6 months

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Primary Outcomes

Description: Number of participants in dose escalating arm with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

Measure: Safety and tolerability of T3011 in dose escalating administration in patients with advanced cutaneous or subcutaneous malignancies

Time: From first dose of T3011 (Week 1 Day 1) until 60 days after the last T3011 injection (up to 2 years)

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Description: Number of participants in dose expansion arm with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

Measure: Safety and tolerability of T3011 in dose expansion administration in patients with advanced cutaneous or subcutaneous malignancies

Time: From first dose of T3011 (Week 1 Day 1) until 60 days after the last T3011 injection (up to 2 years)

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Secondary Outcomes

Description: To evaluate the virus shedding following intratumoral injection

Measure: Presence and frequency of T3011 in serum, saliva, urine, and injection site/dressing

Time: Up to 24 months

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Description: To evaluate IL-12 and anti-PD-1 antibody expression of T3011 post intervention.

Measure: Quantitative measurements of serum IL-12 and anti-PD-1 antibody concentration.

Time: Up to 24 months

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Description: To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 post intervention.

Measure: Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development

Time: Up to 24 months

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Description: To evaluate the immunogenicity of T3011 viral vector post intervention.

Measure: Presence of anti-herpes simplex virus type 1 (HSV-1) antibody compared to baseline

Time: Up to 24 months

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Description: ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Measure: Overall response rate (ORR)

Time: Up to 24 months

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Description: DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments per RECIST 1.1.

Measure: Disease control rate (DCR)

Time: Up to 24 months

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Description: DOR is defined as the time from the first met CR or PR until disease progression or death due to any cause, whichever occurs first.

Measure: Duration of response (DOR).

Time: Up to 24 months

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Description: DR is defined as objective response (CR or PR) according to RECIST 1.1, with a duration of at least 6 months.

Measure: Durable response (DR)

Time: Up to 24 months

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Description: To evaluate the progression free survival (PFS) and overall survival (OS) of participants.

Measure: Survival (assessment per RECIST 1.1 and immune-modified RECIST (imRECIST)).

Time: Up to 24 months

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Primary Outcomes

Measure: Clinical outcome as evaluated by the 7-category Clinical Status Ordinal Scale

Time: At least 60 days, up to 1 year

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Primary Outcomes

Description: This refers to the frequency of grade 3 or 4 AEs considered to be possibly, probably or definitely related to the treatment regimen. Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE version [v] 5.0).

Measure: Incidence of adverse events (AEs)

Time: Up to 30 days post treatment intiation

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Description: will be evaluated based on quantitative polymerase chain reaction PCR

Measure: Kinetics of viral load in nasopharyngeal swabs

Time: Up to 30 days post treatment initiation

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Secondary Outcomes

Description: Will be analyzed using quantitative polymerase chain reaction (PCR).

Measure: Kinetics of viral load in the peripheral blood and nasopharyngeal swabs

Time: During the course of treatment up to day 30

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Description: The circulatory inflammatory mediators include C-reactive protein (CRP), cytokines, chemokines, interferons.

Measure: Kinetics of changes of the immune subsets and circulating inflammatory mediators in peripheral blood

Time: During the course of treatment up to day 30

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Description: The binary endpoint of 30-day mortality will be analyzed using a logistic regression model.

Measure: 30-day mortality

Time: At 30 days post treatment initiation

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Description: Rate of hospitalization due to infection

Measure: Hospitalization due to infection

Time: Up to 30 days post treatment initiation

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Description: Will be tested in nasopharyngeal swabs and blood cells of patients

Measure: Determine known mediators of antiviral immunity

Time: UP to 30 days post treatment initiation

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Other Outcomes

Description: ARDS will be defined by Berlin criteria

Measure: acute respiratory distress syndrome (ARDS)

Time: Up to 30 days post treatment initiation

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Description: Need for mechanical ventilation

Measure: respiratory failure requiring mechanical ventilation

Time: up to 30 days post treatment initiation

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Primary Outcomes

Description: Incidence of cases of MPN patients with COVID-19 experiencing pulmonary embolism

Measure: pulmonary embolism (PE)

Time: 2 and a half months

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Secondary Outcomes

Description: Incidence of cases reporting at least one fatal or non fatal thrombotic event reported in therapy of MPN

Measure: fatal or non fatal thrombotic event

Time: 2 and a half months

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Description: Incidence of cases reporting at least one COVID-19 worsening outcome as Continuous Positive Airway Pressure (CPAP)

Measure: Continuous Positive Airway Pressure (CPAP)

Time: 2 and a half months

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Description: Incidence of cases reporting at least one COVID-19 worsening outcome as invasive ventilation

Measure: invasive ventilation

Time: 2 and a half months

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Description: Incidence of cases reporting at least one COVID-19 worsening outcome as Intensive Care Unit (ICU)

Measure: admission in Intensive Care Unit (ICU)

Time: 2 and a half months

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Description: incidence of death

Measure: death

Time: 2 and a half months

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Description: Type of treatments and interventions applied for MPN during COVID-19 and any change reported in therapy of MPN

Measure: treatments and interventions applied for MPN

Time: 2 and a half months

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Description: Type of treatments and interventions applied for COVID-19

Measure: treatments and interventions applied for COVID-19

Time: 2 and a half months

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Description: Odds Ratios (ORs) of the outcome and 95% Confidence Intervals (CIs) associated with patients' characteristics and treatments

Measure: thrombotic events association to patients characteristic and treatments

Time: 2 and a half months

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Primary Outcomes

Description: Distinguish the likelihood of severe COVID19 (for example, requiring hospitalization, requiring intensive care unit [ICU] treatment or requiring a ventilator) and death due to COVID-19 for patients with versus without the factor. Among subgroups of at least 50 patients, evaluate using chi-square tests as well as death and hospitalization rates.

Measure: Patient variables (factors) associated with severe acute respiratory syndrome (SARS) coronavirus 2 (COVID-19) severity

Time: Up to 2 years

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Description: Describe the degree to which COVID-19 interrupts, delays, or otherwise alters cancer treatment for subgroups of patients defined by cancer type and/or treatment modality. Describe the association between changes in cancer therapy and clinical outcomes. Evaluate association of COVID-19 with outcome by comparison to historical controls in subgroups of at least 50 patients using log rank tests to assess time to survival event.

Measure: Effects of COVID-19 on cancer therapy and association with clinical outcomes

Time: Up to 2 years

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Other Outcomes

Description: Analysis will include time to development of antibodies, prevalence of cytokine abnormalities, and genome-wide association study (GWAS) to define genetic polymorphisms associated with severe COVID-19 disease/mortality.

Measure: Collection of blood specimens for future biomarker studies

Time: Up to 2 years

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Primary Outcomes

Description: Locally evaluated rate of viral response. Favorable response is defined as (1) complete response : negative PCR (absence of detectable signal with a minimum of 40 cycles) or (2) major response : detectable signal but with an increased number of cycles > or egal to 10 compared to initial PCR. Response failure is defined as (1) minor response : detectable signal but with an increased number of cycles < 10 compared to initial PCR or (2) stabilisation or worsening of the viral load.

Measure: Evaluation of the efficacy of hydroxychloroquine and azithromyncine on the viral load drop at day 5.

Time: 5 days of treatment

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Secondary Outcomes

Description: Duration of fever - duration of respiratory symptoms (cough, dyspnea) - duration of other COVID-19 related symptoms (digestive symptoms, ageusia, anosmia)

Measure: Clinical evolution

Time: up to 3 months

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Description: Less or equal to 94% oxygen saturation - need to initiate oxygenotherapy - occurrence of respiratory distress - patient transfer in intensive care unit - need of mechanical ventilation - occurrence of non-respiratory organ failure - occurrence of septic shock

Measure: Proportion of patients progressing to a severe form

Time: up to 3 months

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Description: Date and cause of death

Measure: Mortality

Time: up to 1 and 3 months

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Description: SARS-CoV-2 viral load by PCR on nasopharyngeal swab at day 10 (if positive at day 5) : rate of negativation and comparison of number of cycles with previous samples

Measure: Evaluation of viral load drop

Time: at day 10

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Description: Frequence and causality of all-grade cardiac adverse events - frequence and causality of grade > 1 adverse events for other adverse events - frequence and causality of serious adverse events (CTCAE v5)

Measure: Tolerance of study treatment

Time: up to 3 months

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Description: Collection of serum to realize serological tests

Measure: Evaluation of the seroconversion

Time: at inclusion, day 10, day 30 and day 90 after treatment

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Description: Phenotypic and functional study of NK lymphocytes at inclusion, Retrospective analysis on frozen cells.

Measure: NK immunological study

Time: at day 10 and day 30 after treatment

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Description: Duration of hospitalisation (conventional, intensive care, reanimation)

Measure: Hospitalisation duration

Time: up to 3 months

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Description: Patient follow-up during 3 months : hematological status and associated therapy

Measure: Impact of the study treatment on the treatment of the hematological disease

Time: up to 3 months

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Description: ECG (using connected machine to allow monitoring at home)

Measure: Monitoring of the QT space

Time: at inclusion, day 2, day 5, day 10

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Description: Dosage of residual concentration of azithromycine and hydroxychloroquine.

Measure: Dosage of residual concentration of azithromycine and hydroxychloroquine.

Time: at day 5 and day 10

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Description: Phenotypic and functional study of T lymphocytes at inclusion, Retrospective analysis on frozen cells.

Measure: T immunological study

Time: at day 10 and day 30 after treatment

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Primary Outcomes

Description: To focus on basic issues encountered by oncology patients such as transportation, medical facility, healthcare support, disease apprehension etc

Measure: Oncology patients

Time: 4-8 weeks

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Primary Outcomes

Description: Describe the incidence of patients with a positive test for SARS-CoV-2, detected in the preoperative screening program in our center

Measure: Incidence of patients with a positive test for SARS-CoV-2, detected in the preoperative screening program

Time: May- December 2020

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Secondary Outcomes

Description: Describe the incidence of SARS-CoV-2 infection in the postoperative period in patients with negative screening test.

Measure: Incidence of SARS-CoV-2 infection in the postoperative period in patients with negative screening test;

Time: Up to 30 days

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Description: Postoperative complications will be recorded, according to the Clavien-Dindo classification.

Measure: Postoperative complications

Time: Up to 30 days

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Description: To evaluate the risk of all-cause mortality

Measure: Mortality

Time: 30 days

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Description: Assess the impact of delayed cancer treatment

Measure: Delay in the cancer treatment

Time: May 2020- March 2021

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Primary Outcomes

Description: Evaluation of the proportion of patients with COVID-19 infection's symptoms known to be associated with COVID-19 diagnosis (fever, cough, loss of taste and smell, sore throat, muscle pain, diarrhea, fatigue, difficulty eating and drinking and shortness of breath) followed during a period of 6 months.

Measure: COVID-19 infection's symptoms

Time: Observational period of 6 months

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Secondary Outcomes

Description: To assess the prevalence and course of symptoms of COVID-19 infection of patients followed during a period of 6 months.

Measure: Incidence and course of symptoms of COVID-19 infection

Time: During a period of 6 months

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Description: To establish the correlation of the COVID-19 infection with the biological and clinical data of patients from the Oncology cohort of the Groupe hospitalier Paris Saint-Joseph in Paris followed during a period of 6 months.

Measure: Correlation of the COVID-19 infection with the biological and clinical data of patients

Time: After a period of 6 months

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Primary Outcomes

Description: Associations between baseline characteristics and the primary endpoint will be evaluated with logistic regression, adjusting for arm. These analyses will be largely descriptive, as a result of a limited sample size.

Measure: Proportion of patients with diminished respiratory failure and death

Time: During hospitalization for COVID-19 infection or within 30 days of registration

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Measure: Death

Time: During hospitalization for COVID-19 infection or within 30 days of registration

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Secondary Outcomes

Description: Fever-free will be assessed by a temperature of < 100.5 degrees Fahrenheit orally. Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.

Measure: Time from study initiation to 48 hours fever-free

Time: Up to 14 days

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Description: Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.

Measure: Duration of hospitalization

Time: Up to 14 days

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Measure: Time in intensive care unit (ICU)

Time: Up to 14 days

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Measure: Time to ICU admission

Time: Up to 14 days

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Measure: Number of days requiring supplemental oxygen

Time: Up to 14 days

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Measure: Total days of mechanical ventilation

Time: Up to 14 days

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Measure: Time to mechanical ventilation

Time: Up to 14 days

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Measure: Shock and need for pressure support

Time: Up to 14 days

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Measure: Incidence of any infection (viral, fungal, bacterial)

Time: Up to 14 days

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Measure: Time to clinical resolution

Time: Up to 14 days

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Description: Adverse events will be summarized by grade, type, and attribution (regardless of attribution and treatment-related) for each arm.

Measure: Incidence of grade 3 or higher adverse events

Time: Up to 12 months

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Description: The proportion of patients with viral clearance at the time of hospital discharge will be estimated with 95% confidence intervals for each arm.

Measure: At the end of therapy (day 14)

Time: Up to 14 days

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Description: Will be estimated for each arm using the method of Kaplan-Meier. Medians estimates and/or estimates at specific time points will be provided with 95% confidence intervals.

Measure: Time to viral clearance

Time: Up to 12 months

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Description: Patients will be followed for up to 12 months or until death or withdrawal of study consent for further follow-up. Following hospitalization, study visits will be telephone or video encounters.

Measure: Survival

Time: Up to12 months

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Primary Outcomes

Description: Will be compared to the time of randomization. The severity of symptoms will be categorized as mild, moderate, severe, or critical according to the grading of symptoms. The proportion of participants with progression to more severe symptoms between treatments groups will be compared using a Fisher's Exact test at a 0.05 significance level.

Measure: Severity of symptoms

Time: 3 months

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Secondary Outcomes

Description: Will be defined as improvement on symptoms: yes or no. Will be compared between treatment groups using log-rank test. A 95% confidence interval of treatment rate difference in symptom progression will be calculated by the Wald method.

Measure: Clinical benefit rate of lopinavir/ritonavir

Time: 3 months

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Description: Will be compared between treatment groups using log-rank test.

Measure: Time to symptom progression

Time: From randomization to the first documented symptoms progression, assessed up to 3 months

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Description: Will be compared between treatment groups using log-rank test.

Measure: Time to improvement of participants

Time: From randomization to first documented complete resolution of symptoms, assessed up to 3 months

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Description: Will be compared between treatment groups using log-rank test.

Measure: Time to hospital admission for those who develop severe of critical symptoms

Time: From time of randomization to the time of hospital admission, assessed up to 3 months

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Description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.

Measure: Intensive care unit (ICU) admission: yes or no

Time: 3 months

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Description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.

Measure: Receiving ventilator support: yes or no

Time: 3 months

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Description: Will be compared using Fisher's exact test, and point and interval estimates will be provided.

Measure: Overall survival

Time: From randomization to death due to any cause, assessed up to 3 months

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Other Outcomes

Description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.

Measure: Potassium level

Time: 3 months

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Description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.

Measure: Blood oxygen level

Time: 3 months

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Description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.

Measure: Creatinine level

Time: 3 months

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Description: Will be compared between treatments group using t-test or non-parametric comparison if the distribution of lab values are deviated from normal distribution. The proportion of participants of whom lab values are obtained will be tabulated and compared using the chi-square test.

Measure: Blood pressure

Time: 3 months

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Description: Will evaluate on a subjective basis the ability to remotely consent, monitor and treat patients in the context of a pandemic of a contagious disease. The proportion of participants able to be remotely consented, monitored, and treated in the context of a pandemic of a contagious disease will be tabulated and compared using the chi-square test.

Measure: Ability to remotely consent, monitor, and treat patients in the context of a pandemic of a contagious disease

Time: 3 months

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Primary Outcomes

Description: Retrospective chart review of health care utilization of both groups

Measure: Health Care Utilization Comparison

Time: 5 months

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Secondary Outcomes

Description: Patient Reported Outcomes Measurement Information System- Short Form v2.0 Social Isolation- 6a. The PROMIS Social Isolation item bank assesses perceptions of being avoided, excluded, detached, disconnected from, or unknown by, others. The item bank does not use a time frame (e.g. over the past seven days) when assessing social isolation. A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like Social Isolation, a T-score of 60 is one SD worse than average. By comparison, a Social Isolation Tscore of 40 is one SD better than average.

Measure: Patient Social Isolation

Time: Monthly for 5 months

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Description: Patient reported outcomes collected in automated SCH system daily of COVID-19 symptoms, social distancing and hygiene practices, and COVID-19 related cancer treatment impacts and daily living impacts on cancer patients receiving the SCH -COVID intervention. The investigators will describe patterns of cancer patients and their adherence to social distancing and hygiene practices over time.

Measure: COVID-19 Symptoms, Social distancing and Hygiene Practices

Time: Daily for 5 months

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Description: Patient Reported Outcomes Measurement Information System Scale v1.2- Global Health Survey Short Form 10. High scores reflect better functioning. To find the total raw score for these scales with all questions answered, sum the values of the response to each question for a given respondent.

Measure: Patient Global Health

Time: Monthly 5 months

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Description: Hospital Anxiety and Depression Scale (HADS) measurement of psychological distress in non-psychiatric patients.

Measure: Patient Anxiety/Depression

Time: Monthly 5 months

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Description: COVID-19: Impact of the Pandemic and Health Related Quality Of Life (HRQOL) in Cancer Patients and Survivors

Measure: Impact of Pandemic and Health Related Quality of Life

Time: Baseline then 3 months and 5 months from baseline

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Description: Patient reported outcomes collected in automated SCH system daily of cancer symptom severity on a scale of 0-10 with 0 being no pain and 10 being worst pain imaginable. Description of symptom severity over time will be reported

Measure: Cancer symptom severity

Time: Daily for 5 months.

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Primary Outcomes

Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: Experiences during the coronavirus disease 2019 (COVID-19) pandemic

Time: 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific psychological distress

Time: Up to 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific health

Time: Up to 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific financial and social disruptions

Time: Up to 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific perceived benefits and social support

Time: Up to 2 months

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Description: This will be measure with a COVID-19 questionnaire created to collect COVID-19 experience information, Quality of life (QOL), and other psychosocial variables from participating patients. Using this questionnaire may help researchers gain an understanding of how experiences during the COVID-19 pandemic (e.g., exposure, risk factors, testing,isolation,seropositivity, hospitalization, loss of family or friends, loss of income), may impact multiple domains of health-related quality of life (physical, emotional and social well-being), and other areas such as COVID-19-specific psychological distress (e.g., fear, anxiety and depressive symptoms), and disruptions to health care, finances, and social interactions.

Measure: COVID-19-specific health related quality of life (HRQoL)

Time: Up to 2 months

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Description: Will evaluate the extent to which resiliency factors such as social support and perceived benefits moderate the effects of COVID-19 experiences on COVID-19-specific psychological distress and HRQoL.

Measure: Effects of COVID-19 experiences on COVID-19-specific psychological distress and HRQoL

Time: Up to 2 months

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