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Report for Clinical Trial NCT02011945

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1B Dose Escalation Study to Investigate the Safety, Tolerability and Preliminary Efficacy for the Combination Dasatinib (BMS-354825) Plus Nivolumab (BMS-936558) in Patients Chronic Myeloid Leukemia (CML)

The purpose of this study is to find a dose of Nivolumab that can be safely added to Dasatinib in patients with Chronic Myeloid Leukemia.

NCT02011945 Chronic Myeloid Leukemia
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

2 Interventions

Name: Dasatinib

Type: Drug

Dose Level 1 Dose Level 2 dasatinib Only

Name: Nivolumab

Type: Drug

Dose Level 1 Dose Level 2


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There are 2 SNPs

SNPs


1 T315A

T315I or T315A) For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. --- T315I --- --- T315A ---

T315I or T315A) Chronic Myeloid Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive null --- T315I --- --- T315A ---


2 T315I

T315I or T315A) For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. --- T315I ---

T315I or T315A) Chronic Myeloid Leukemia Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive null --- T315I ---



HPO Nodes


HPO:
Chronic myelogenous leukemia
Genes 9
KIT MPL ASXL1 TET2 ABL1 JAK2 THPO BCR SRSF2
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Myeloid leukemia
Genes 20
KIT SETBP1 NF1 ARHGAP26 CBL TET2 KRAS PTPN11 F13A1 SAMD9L SAMD9L GATA2 CBL ASXL1 DNMT3A F13B NRAS SRSF2 TERC TERT