Primary Outcomes

Description: The following drug-related adverse events (AEs) occurring in the first 28 days of treatment were considered dose-limiting toxicities (DLT): Grade 4 hematologic AE lasting >7 days; ≥Grade 3 nonhematologic AE, despite medical intervention; ≥Grade 2 AE uncontrolled by medical intervention and requiring treatment interruption for >7 days. RP2D was that dose at which ≤1 of 6 patients had a DLT in the first 4 weeks of treatment. If <3 patients were DLT-evaluable, up to 6 additional patients entered the same dose level. Accrual to a dose level closed if 6 patients were enrolled and <3 were DLT-evaluable. If ≥3 patients at a dose level had no DLTs when a new patient enrolled, the dose was escalated to next level. If 1 DLT was observed in <6 patients, ≥6 patients were required; if no additional DLT was observed, the dose was escalated to the next highest level. If ≥2 DLTs were observed in <6 patients, that level exceeded the RP2D, and the dose was deescalated to the next lowest level.

Measure: Recommended Phase 2 Dose (RP2D) of BMS-833923 Plus Dasatinib in Chronic Myeloid Leukemia-Chronic Phase

Time: Day 1 to Week 80, with observation for DLT in Weeks 5-8

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Secondary Outcomes

Description: Cytogenetic response (CyR) was based on the proportion of Philadelphia chromosome-positive (Ph+) cells in metaphase analysis of bone marrow. Complete cytogenetic response (CCyR)=0 Ph+ cells; Partial CyR (PCyR)=1 to 35 Ph+ cells; Minor CyCR= 36-65 Ph+ cells; Minimal CyCR= 66-95 Ph+ cells; No response= >96 Ph+ cells. MCyR=CCyR + PCyR. Nilo=nilotinib; SOR=suboptimal response.

Measure: Percentage of Participants With a Major Cytogenetic Response (MCyR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP)

Time: Day 1 to Week 80

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Description: MHR was defined as complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR for CML-Adv criteria: white blood cell count (WBC) ≤upper limit normal; absolute neutrophil count (ANC) ≥1,000/mm^3; platelets ≥100,000/mm^3; no blasts or promyelocytes in peripheral blood (PB); basophils <5% in PB; myelocytes + metamyelocytes < 5% in PB; no extramedullary involvement; blasts must be <5%, if bone marrow assessment (BMA) performed. NEL had same criteria, but with lower thresholds for reconstitution of PB counts, as follows: Platelets ≥ 20,000/mm^3 or ANC >500/mm^3. Confirmed MHR obtained if these criteria met and maintained for ≥28 days. CHR for CML-CP criteria WBC ≤10,000/mm^3; platelets <450,000/mm^3; basophils <5% in PB; no blasts or promyelocytes in PB; myelocytes + metamyelocytes <5% in PB; no extramedullary involvement; blasts must be <5% if BMA performed. Confirmed CHR obtained if these criteria met and maintained for ≥28 days. Nilo=nilotinib; SOR=suboptimal response.

Measure: Percentage of Participants With a Major Hematologic Response (MHR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP)

Time: Day 1 to Week 80

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Description: AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment and may or may not be related to treatment. SAE=an untoward medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug. The following drug-related AEs occurring during the first 28 days of treatment with both agents were considered to be dose-limiting toxicities (DLTs): Grade 4 hematologic AE lasting >7 days; ≥Grade 3 nonhematologic AE, despite adequate medical intervention; ≥Grade 2 AE not controlled by medical intervention and requiring treatment interruption for >7 days.

Measure: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities

Time: Day 1 to Week 80, continuously, with observation for dose-limiting toxicities (DLTs) in Weeks 5-8

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Description: ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal. Abnormalities were graded according to the Common Toxicity Criteria of the National Cancer Institute from 1 (least severe) to 4 (life threatening). ANC (*10^9): Grade 3, <1.0- 0.5; Grade 4, <0.5. Hemoglobin (mmol/L): Grade 3, <4.9-4.0; Grade 4, <4.0. Platelet count (*10^9/L): Grade 3, <50.0-25.0; Grade 4, <25. WBCs (*10^9): Grade 3, <2.0-1.0; Grade 4, <1.0. Hypocalcemia (mmol/L): Grade 3, <1.75-1.5; Grade 4, <1.5. Hyperkalemia (mmol/L): Grade 3, >6.0-7.0; Grade 4, >7.0. Hypokalemia (mmol/L): Grade 3, <3.0-2.5; Grade 4, <2.5. Hyponatremia (mmol/L), Grade 3, <130-120; Grade 4, <120. Hypermagnesemia (mg/dL): Grade 3, >1.23-3.30; Grade 4, >3.30. Phosphorus (mmol/L): Grade 3, <0.6-0.3; Grade 4, <0.3. Lipase (*ULN): Grade 3, >2.0-5.0; Grade 4, >5.0.

Measure: Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results

Time: Day 1 to Week 80

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Primary Outcomes

Description: Major molecular response (MMR) was assessed using BCR-ABL transcript levels measured by real-time quantitative polymerase chain reaction (qPCR). MMR was defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value). Number of participants with MMR by timepoint are cumulative.

Measure: Number of Participants With Major Molecular Response

Time: Baseline up to 12 months

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Secondary Outcomes

Measure: Complete Molecular Response at Any Time

Time: Baseline to End of study (approximately 48 months)

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Measure: Progression-free Survival, Measured by the Time From Start of Treatment to Progression or Death

Time: Baseline to End of study (approximately 48 months)

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Measure: Event-free Survival, Measured by the Time From Start of Treatment to Progression, Death or Treatment Discontinuation

Time: Baseline to End of study (approximately 48 months)

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Measure: Transformation-free Survival Measured by the Time From Start of Treatment to Criteria for Accelerated or Blast Phase CML Are Met and Death

Time: Baseline to End of study (approximately 48 months)

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Description: AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug.

Measure: Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death

Time: From date of first dose of study treatment up to the date of the last dose plus 30 days (approximately 49 months)

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Primary Outcomes

Description: Maximum Tolerated Dose (MTD) of Ruxolitinib with fixed dose of Nilotinib. Dose escalation will follow a 3+3 study design. The CTCAE v4.03 criteria will be used. Grade 4 toxicity will be accounted as dose limiting toxicity (DLT).

Measure: Phase I: Maximum Tolerated Dose (MTD)

Time: Average of 6 months

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Description: Major cytogenetic response defined by 35% or less of Philadelphia chromosomes by metaphase cytogenetics in marrow from CML and ALL patients

Measure: Phase II: Major cytogenetic response

Time: Average of 6 months

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Secondary Outcomes

Description: Complete hematologic response defined by CBC differential without any evidence of leukemia. It will be evaluated in CML patients in AP or BP, and patients with Ph+ ALL.

Measure: Phase I: complete hematologic response

Time: Average of 3 months

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Description: Major cytogenetic response defined by 35% or less of Philadelphia chromosomes by metaphase cytogenetics in marrow taken at 6 months.

Measure: Phase I: major cytogenetic response

Time: Average of 6 months

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Description: It will be defined by NCI Common Terminology Criteria for Adverse Events (CTCAE)version 4.03 for adverse event reporting.

Measure: Phase I: Safety and tolerability

Time: Average of 6 months

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Description: Complete hematologic response defined by CBC differential without any evidence of leukemia. It will be evaluated in the CML patients in AP or BP and in patients with Ph+ ALL.

Measure: Phase II: complete hematologic response

Time: Average of 3 months

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Other Outcomes

Description: Cmax will be measured for the maximum plasma concentration of nilotinib after oral administration.

Measure: Phase II (exploratory): pharmacokinetic profile of combination of Nilotinib with Ruxolitinib

Time: During first 24 hours of first dose

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Primary Outcomes

Description: DLT will be determined based on the incidence and intensity of drug related adverse events (AEs). The following drug-related AEs (whether related to one or both agents) occurring during the first 6 weeks of combined treatment with both dasatinib plus nivolumab (ie, Weeks 3 to 8, inclusive) would be considered DLTs: Grade 4 hematologic AE lasting > 7 days despite appropriate medical intervention, except as noted below; Grade 3 or Grade 4 nonhematologic AE irrespective of duration; Grade 2 nonhematologic AE lasting > 7 days despite appropriate medical intervention (exception: asymptomatic laboratory values of Grade 2 which do not require medical intervention); Any toxicity managed by discontinuation of nivolumab; Grade ≥ 2 AE not controlled by medical intervention and requiring dasatinib treatment interruption for > 28 consecutive days; Grade ≥ 2 AE not controlled by medical intervention and requiring missing 2 consecutive doses of nivolumab.

Measure: Incidence of Dose Limiting Toxicities (DLT)

Time: Week 3 to week 6

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Description: Any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product.

Measure: Incidence of Adverse Events (AEs)

Time: Initiation of study drug to discontinuation of nivolumab stop date + 100 days or discontinuation of dasatinib + 30 days

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Description: Any untoward medical occurrence that at any dose: results in death, is life threatening, requires in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is a important medical event.Requires inpatient hospitalization or causes prolongation of existing hospitalization, results.

Measure: Incidence of Serious Adverse Events (SAEs)

Time: Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing

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Description: The number of participants with a shift in laboratory test results from baseline to Grade 3-4 in hematology

Measure: Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology

Time: Up to 40 Months

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Description: The number of participants with an abnormal Liver function test. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)

Measure: Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests

Time: Up to 40 Months

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Description: Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)

Measure: Incidence of Laboratory Abnormalities in Specific Thyroid Tests

Time: Up to 40 Months

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Secondary Outcomes

Description: Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).

Measure: Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants

Time: upto 36 Months

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Description: Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).

Measure: Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants

Time: upto 36 Months

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Description: Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).

Measure: Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants

Time: upto 36 Months

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Description: Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).

Measure: Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants

Time: upto 36 Months

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Description: Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).

Measure: Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants

Time: upto 36 Months

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Description: Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).

Measure: Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants

Time: upto 36 Months

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Description: measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

Measure: Time to Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants

Time: Up to 36 Months

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Description: measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

Measure: Time to Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants

Time: Up to 36 Months

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Description: measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

Measure: Time to Major Molecular Response (MMR) - CML-AP Participants

Time: Up to 36 Months

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Description: will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

Measure: Duration of Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants

Time: Up to 36 Months

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Description: will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

Measure: Duration of Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants

Time: Up to 36 Months

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Description: will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

Measure: Duration of Major Molecular Response (MMR) - CML-AP Participants

Time: Up to 36 Months

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Description: measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

Measure: Time to Molecular Response 4.5(MR4.5) - CML-CP No Prior Dasatinib Participants

Time: Up to 36 Months

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Description: measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

Measure: Time to Molecular Response 4.5(MR4.5) - CML-CP Prior Dasatinib Participants

Time: Up to 36 Months

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Description: measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

Measure: Time to Molecular Response 4.5(MR4.5) - CML-AP Participants

Time: Up to 36 Months

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Description: will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

Measure: Duration of Molecular Response 4.5 (MR4.5) - CML-CP No Prior Dasatinib Participants

Time: Up to 36 Months

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Description: will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

Measure: Duration of Molecular Response 4.5 (MR4.5) - CML-CP Prior Dasatinib Participants

Time: Up to 36 Months

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Description: will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

Measure: Duration of Molecular Response 4.5 (MR4.5) - CML-AP Participants

Time: Up to 36 Months

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Primary Outcomes

Description: is to be evaluated by using a combination of criteria. Molecular remissions will be defined by standard criteria for BCR-ABL1 and IGH qRT-PCR. Flow cytometric assessment of MRD will be defined by standard flow cytometry criteria

Measure: Clinical response

Time: 2 years

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Secondary Outcomes

Description: Molecular remission status will be defined by undetectable BCR-ABL1 transcripts and/or IGH clonal gene rearrangement in bone marrow aspirate (BMA) examination as determined by qRT-PCR in CLIA laboratory.

Measure: Complete Molecular Remission (CMR) rate

Time: 2 years

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