Name (Synonyms) | Correlation | |
---|---|---|
drug83 | ASP7517 Wiki | 0.58 |
drug2830 | granulocyte colony-stimulating factor (G-CSF) Wiki | 0.58 |
drug1154 | IO-202 Dose Escalation Wiki | 0.58 |
drug2823 | fludarabine Wiki | 0.58 |
drug1156 | IO-202 Dose Expansion B Wiki | 0.58 |
drug1155 | IO-202 Dose Expansion A Wiki | 0.58 |
drug2828 | gilteritinib Wiki | 0.58 |
drug2795 | cytarabine Wiki | 0.58 |
Name (Synonyms) | Correlation | |
---|---|---|
D007951 | Leukemia, Myeloid, NIH | 1.00 |
D015470 | Leukemia, Myeloid, Acute NIH | 0.87 |
D007938 | Leukemia, NIH | 0.71 |
D015477 | Leukemia, Myelomonocytic, Chronic NIH | 0.58 |
D011289 | Preleukemia NIH | 0.41 |
D009190 | Myelodysplastic Syndromes NIH | 0.33 |
D013577 | Syndrome NIH | 0.06 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0004808 | Acute myeloid leukemia HPO | 0.87 |
HP:0012325 | Chronic myelomonocytic leukemia HPO | 0.58 |
HP:0001909 | Leukemia HPO | 0.48 |
HP:0002863 | Myelodysplasia HPO | 0.33 |
There are 3 clinical trials
The purpose of this study is to evaluate the safety and tolerability and to determine the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) of ASP7517. This study will also evaluate the clinical response of ASP7517 as well as other measures of anticancer activity of ASP7517.
Description: A DLT is defined as any of the following events that occur within 28 days starting with the first dose on cycle 1 day 1 (C1D1) and that is considered to be related to investigation product (IP). The severity of AEs will be assessed according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. DLT is defined as follows: non-hematologic AEs that are ≥ grade 3; confirmed Hy's law case; new onset of grade 4 thrombocytopenia (with minimum of 2 grade worsening from baseline) within 24 hours of dosing; prolonged myelosuppression, defined as absolute neutrophil count (ANC) < 500/μL for more than 28 days off therapy and in the absence of evidence of active leukemia or MDS in the marrow or blood, will be considered as a DLT.
Measure: Incidence of dose limiting toxicities (DLTs) Time: 28 daysDescription: An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. 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 whether or not considered related to the medicinal product. AEs will be graded using NCI-CTCAE guidelines, version 5.0.
Measure: Number of participants with adverse events (AEs) Time: Up to 2 yearsDescription: An AE is considered "serious" if the event: results in death; is life-threatening (An AE is considered "life-threatening" if its occurrence places the subject at immediate risk of death; it does not include an AE that, had it occurred in a more severe form, might have caused death.); results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly, or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); other medically important events.
Measure: Number of participants with serious adverse events (SAEs) Time: Up to 2 yearsDescription: Number of participants with potentially clinically significant laboratory values.
Measure: Number of participants with laboratory value abnormalities and/or AEs Time: Up to 2 yearsDescription: Routine 12-lead ECGs will be taken after the subject has been resting in the supine position for at least 5 minutes. Routine 12-lead ECGs will be taken in triplicate.
Measure: Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs Time: Up to 2 yearsDescription: Number of participants with potentially clinically significant vital sign values.
Measure: Number of participants with vital sign abnormalities and/or AEs Time: Up to 2 yearsDescription: Number of participants with potentially clinically significant physical exam values.
Measure: Number of participants with physical exam abnormalities and/or AEs Time: Up to 2 yearsDescription: The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Measure: Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status Time: Up to 2 yearsDescription: CRc rate is defined for AML subjects as the number of participants who achieve the best response of CRc (complete response [CR], complete remission with incomplete platelet recovery [CRp] or complete remission with incomplete hematological recovery [CRi]) divided by the number of participants in the analysis population.
Measure: Composite complete remission (CRc) rate for participants with R/R AML (phase 2) Time: Up to 2 yearsDescription: Complete response + bone marrow complete response + partial response (CR + BM CR + PR) rate for participants with R/R higher risk MDS (phase 2) [ Time Frame: Up to 2 years ] CR + BM CR + PR rate is defined for MDS participants as the number of participants who achieve the best response of CR + BM CR + PR divided by the number of subjects in the analysis population.
Measure: Complete response + bone marrow complete response + partial response (CR + BM CR + PR) rate for participants with R/R higher risk MDS (phase 2) Time: Up to 2 yearsDescription: Duration of remission for participants with AML includes duration of CRc, duration of CR/complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR, and duration of response (i.e., CRc + PR).
Measure: Duration of remission for participants with AML Time: Up to 2 yearsDescription: Duration of remission for MDS includes duration of CR and duration of response (i.e., CR + PR).
Measure: Duration of remission for participants with MDS Time: Up to 2 yearsDescription: EFS is defined as the time from the date of first dose until the date of documented relapse, treatment failure or death from any cause within 30 days after the last dose of study drug (whichever occurs first earliest of [relapse date, treatment failure date, death date] - first dose date + 1).
Measure: Number of participants with event-free survival (EFS) Time: Up to 2 yearsDescription: OS is defined as the time from the date of first dose until the date of death from any cause (death date - first dose date + 1).
Measure: Duration of overall survival (OS) Time: Up to 2 yearsDescription: CR rate is defined as the number of participants who achieve CR at any of the postbaseline visits divided by the number of participants in the analysis population.
Measure: CR rates for participants with R/R AML Time: Up to 2 yearsDescription: Best response rate is defined as the number of subjects who achieve CRc or PR at any of the postbaseline visits divided by the number of subjects in the analysis population.
Measure: Best response (CRc + PR) rates for participants with R/R AML Time: Up to 2 yearsDescription: CRh rate is defined as the number of participants who achieve CRh at any of the postbaseline visits divided by the number of participants in the analysis population.
Measure: CRh rates for participants with R/R AML Time: Up to 2 yearsDescription: CR rate is defined as the number of participants who achieve CR at any of the postbaseline visits divided by the number of participants in the analysis population.
Measure: CR rates for participants with R/R higher risk MDS Time: Up to 2 yearsDescription: HI requires 1 measurement of erythroid or platelets or neutrophils maintained at a specified level for at least 8 weeks without ongoing cytotoxic therapy
Measure: Hematologic improvement (HI) rates for participants with R/R higher risk MDS Time: Up to 2 yearsDescription: Objective response (CR + BM CR + PR + HI) rates (ORR) for participants with R/R higher risk MDS [Time Frame: Up to 2 years] ORR is defined as the number of participants who achieve CR or BM CR or PR or HI at any of the postbaseline visits divided by the number of participants in the analysis population.
Measure: Objective response (CR + BM CR + PR + HI) rates (ORR) for participants with R/R higher risk MDS Time: Up to 2 yearsThe purpose of the phase 1 portion (dose escalation) of the study will be to establish an optimally safe and biologically active recommended phase 2 dose (RP2D) and/or to determine maximum tolerated dose (MTD) for gilteritinib in sequential combination with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). The purpose of the phase 2 portion (dose expansion) is to determine complete remission (CR) rates and composite complete remission (CRc) rates after two cycles of therapy. The study will also assess safety, tolerability and toxicities of gilteritinib in combination with FLAG, evaluate FLT3 inhibition, assess pharmacokinetics (PK), perform serial measurements of minimal residual disease, obtain preliminary estimates of 1-year event free survival (EFS) and overall survival (OS) rate and assess the acceptability as well as palatability of the formulation. One cycle is defined as 28 days of treatment. A participant completing 2 cycles in phase 1 or 2 will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).
Description: A DLT is defined as any of the events meeting the DLT criteria that occur during the observation period and that is considered to be possibly or probably related to gilteritinib. Nonhematologic Dose-limiting Toxicity will be defined as grade 3 or 4 nonhematologic toxicity attributable to gilteritinib that persists for > 48 hours without resolution to grade ≤ 2, will have gilteritinib dosing interrupted. Exceptions include the toxicities commonly seen with intensive AML reinduction regimens. Hematologic Dose-limiting Toxicity will be defined as failure to recover a peripheral absolute neutrophil count (ANC) > 500/μL and non-transfusion dependent platelet count > 20000/μL due to documented bone marrow aplasia/hypoplasia for greater than or equal to 50 days from the start of cycle 1 day 1. Failure to recover peripheral counts due to disease involvement of the bone marrow will not be considered dose-limiting toxicity.
Measure: Number of participants with dose limiting toxicity (DLT) (phase 1/dose escalation) Time: Up to 28 daysDescription: CR rate is defined as the number of participants who achieve the best response of CR divided by the number of participants in the analysis population. Complete remission is defined as having bone marrow regenerating normal hematopoietic cells and achieving a morphologic leukemia-free state and must have an absolute neutrophil count (ANC) ≥ 1 x 10^9/L and platelet count ≥ 100 x 10^9/L and normal marrow differential with < 5% blasts, and they will be red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia.
Measure: Complete Remission (CR) rate after 2 cycles of therapy (phase 2) Time: Up to 56 daysDescription: CRc rate is defined as the number of participants who achieve the best response of CRc (CR, CRp,or CRi) divided by the number of participants in the analysis population. Complete remission with incomplete platelet recovery (CRp) is defined as achieving CR except for incomplete platelet recovery (< 100 x 10^9/L) at a post baseline visit. Complete remission with incomplete hematologic recovery (CRi) is defined as achieving CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery at a post baseline visit. Red blood cell (RBC) and platelet transfusion independence is not required.
Measure: Composite complete remission (CRc) rate after 2 cycles of therapy (phase 2) Time: Up to 56 daysDescription: An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. 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 whether or not considered related to the medicinal product.
Measure: Number of participants with Adverse Events (AEs) Time: Up to 2 years plus 28 day follow upDescription: Number of participants with potentially clinically significant vital sign values.
Measure: Number of participants with vital sign abnormalities and /or adverse events (AEs) Time: Up to 2 yearsDescription: Number of participants with potentially clinically significant laboratory values.
Measure: Number of participants with laboratory value abnormalities and/or adverse events (AEs) Time: Up to 2 yearsDescription: Number of participants with potentially clinically significant ECG values.
Measure: Number of participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs) Time: Up to 2 yearsDescription: Inhibition of FLT3 phosphorylation after drug treatment will be determined relative to pre-treatment phosphorylated FLT3 levels in participants to assess the relationship with gilteritinib dose. Phosphorylated FLT3 will be measured by plasma inhibitory activity (PIA) assay.
Measure: Percentage of inhibition of phosphorylated FLT3 in participants. Time: Up to 49 daysDescription: CL/F will be reported from the PK plasma samples collected.
Measure: Pharmacokinetics (PK) of gilteritinib: oral clearance (CL/F) Time: Up to 45 daysDescription: Vd/F will be reported from the PK plasma samples collected.
Measure: PK of gilteritinib: apparent volume of distribution (Vd/F) Time: Up to 45 daysDescription: Cmax will be reported from the PK plasma samples collected.
Measure: PK of gilteritinib: Maximum Concentration (Cmax) Time: Up to 45 daysDescription: tmax will be reported from the PK plasma samples collected.
Measure: PK of gilteritinib: Time of Maximum Concentration (tmax) Time: Up to 45 daysDescription: AUC will be reported from the PK plasma samples collected.
Measure: PK of gilteritinib: Area Under the Concentration (AUC) Time: Up to 45 daysDescription: EFS is defined as the time from the date of enrollment until the date of documented relapse (excluding relapse after PR), treatment failure or death, whichever occurs first. If a participant experiences relapse or death, the participant is defined as having EFS event related to either "relapse" or "death", and the event date is the date of relapse or death. If a participant fails to achieve any of the response of CR, CRp, CRi or PR during the treatment period, the participant is defined as having EFS event related to treatment failure, and the event date is the enrollment date. For a participant who is not known to have had a relapse or treatment failure or death event, EFS is censored at the date of last relapse-free disease assessment. Participant is not censored at hematopoietic stem cell transplant (HSCT).
Measure: Duration of Event Free Survival (EFS) Time: Up to 2 yearsDescription: OS is defined as the time from the date of enrollment until the date of death from any cause. For a participant who is not known to have died by the end-of-study follow-up, OS is censored at the date of last contact.
Measure: Duration of Overall survival (OS) Time: Up to 4 years and 2 monthsDescription: MRD negative status will be defined as FLT3-internal tandem duplication (ITD) signal ratio ≤ 10^-4.
Measure: The number of participants with negative minimal residual disease (MRD) status Time: Up to 2 yearsDescription: MRD negative status will be defined as FLT3-internal tandem duplication (ITD) signal ratio ≤ 10^-4.
Measure: Number of participants with MRD negative status in relation to CR rate Time: Up to 2 yearsDescription: MRD negative status will be defined as FLT3-internal tandem duplication (ITD) signal ratio ≤ 10^-4.
Measure: Number of participants with MRD negative status in relation to CRc rate Time: Up to 2 yearsDescription: MRD negative status will be defined as FLT3-internal tandem duplication (ITD) signal ratio ≤ 10^-4.
Measure: Number of participants with MRD negative status in relation to Overall survival (OS) Time: Up to 2 yearsDescription: The acceptability and palatability of gilteritinib oral formulation as assessed by the participant using a single scale. The 5 point facial hedonic scale has high to low as: Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much.
Measure: Clinical Outcome Assessment of Taste Time: Up to 57 daysTo assess safety and tolerability at increasing dose levels of IO-202 in successive cohorts of participants with relapsed or refractory monocytic AML and CMML in order to estimate the maximum tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended Phase 2 dose (RP2D) and dose schedule as monotherapy and in combination with azacitidine (AZA).
Description: Incidence of adverse events
Measure: Safety of IO-202 as measured by incidence of adverse events. Time: From first dose of IO-202 to 30 days following last study treatmentDescription: Severity of adverse events
Measure: Safety of IO-202 as measured by severity of adverse events. Time: From first dose of IO-202 to 30 days following last study treatmentDescription: Incidence dose interruptions and dose reductions
Measure: Tolerability of IO-202 as measured by incidence and duration of dose interruptions and dose reductions of study treatment Time: From first dose of IO-202 to 30 days following last study treatmentDescription: Maximum concentration (Cmax) of IO-202
Measure: To characterize the pharmacokinetics (PK) of IO-202 as defined by maximum plasma concentration (Cmax) Time: Through study completion, an average of 1 yearDescription: measure area under the curve (AUC) of IO-202
Measure: To characterize the PK of IO-202 as defined by area under the curve (AUC) Time: Through study completion, an average of 1 yearDescription: Measure anti-drug antibodies in plasma.
Measure: To evaluate the incidence of anti-drug antibodies against IO-202 Time: Through study completion, an average of 1 yearDescription: Measure response rates in patients with anti-drug antibodies.
Measure: To measure rates of response to IO-202 in patients with anti-drug antibodies Time: Through study completion, an average of 1 yearDescription: Measure response rates by bone marrow examination of blast percentage.
Measure: Measure response rates in patients treated with IO-202 or IO-202 in combination with AZA Time: Through study completion, an average of 1 yearDescription: Measure changes in numbers of lymphocytes with study drug treatment
Measure: To assess changes in lymphocytes with IO-202 or IO-202 in combination with AZA Time: Through study completion, a average of 1 yearDescription: Measure changes in blood immune proteins with study drug treatment
Measure: To measure blood immune proteins with IO-202 or IO-202 in combination with AZA Time: Through study completion, a average of 1 yearDescription: Statistical correlation levels of target expression on leukemic blasts with response rate
Measure: To correlate target expression with response rates Time: Through study completion, a average of 1 yearDescription: Statistical correlation of target expression on leukemic blasts with adverse event rates
Measure: To correlate target expression with rates of adverse events Time: Through study completion, a average of 1 yearDescription: Measure immunophenotype of leukemic blasts from bone marrow aspirates after study treatment
Measure: To evaluate immunophenotype of leukemic blasts after study treatment. Time: Through study completion, a average of 1 year