A Phase 1B Study to Investigate the Safety and Preliminary Efficacy for the Combination of Dasatinib Plus Nivolumab in Patients With Chronic Myeloid Leukemia
- Registration Number
- NCT02011945
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
-
Confirmed diagnosis of Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase :
- With historically documented Ph+ cells
- ≥2 prior Tyrosine Kinase Inhibitors (TKI) therapies for CML
- Currently progressing, resistance to or with a suboptimal response to their most recent therapy
-
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score 0 - 1
- Blast phase CML
- Known Abl-kinase mutation resistant to Dasatinib (e.g. T315I or T315A)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description dasatinib Only Dasatinib dasatinib 100 mg QD(CP) or 140 mg QD (AP) Dose Level 1 Dasatinib Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Dose Level 1 Nivolumab Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Dose Level 2 Dasatinib Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Dose Level 2 Nivolumab Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
- Primary Outcome Measures
Name Time Method Incidence of Adverse Events (AEs) Initiation of study drug to discontinuation of nivolumab stop date + 100 days or discontinuation of dasatinib + 30 days 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.
Incidence of Serious Adverse Events (SAEs) Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing 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.
Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology Up to 40 Months The number of participants with a shift in laboratory test results from baseline to Grade 3-4 in hematology
Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests Up to 40 Months The number of participants with an abnormal Liver function test.
Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)Incidence of Laboratory Abnormalities in Specific Thyroid Tests Up to 40 Months Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
Incidence of Dose Limiting Toxicities (DLT) Week 3 to week 6 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.
- Secondary Outcome Measures
Name Time Method Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants upto 36 Months 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).Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants upto 36 Months 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).Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants upto 36 Months 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).Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants upto 36 Months 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).Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants upto 36 Months 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).Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants upto 36 Months 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).Time to Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants Up to 36 Months 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.
Time to Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants Up to 36 Months 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.
Time to Major Molecular Response (MMR) - CML-AP Participants Up to 36 Months 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.
Duration of Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants Up to 36 Months 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
Duration of Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants Up to 36 Months 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
Duration of Major Molecular Response (MMR) - CML-AP Participants Up to 36 Months 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
Time to Molecular Response 4.5(MR4.5) - CML-CP No Prior Dasatinib Participants Up to 36 Months 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.
Time to Molecular Response 4.5(MR4.5) - CML-CP Prior Dasatinib Participants Up to 36 Months 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.
Time to Molecular Response 4.5(MR4.5) - CML-AP Participants Up to 36 Months 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.
Duration of Molecular Response 4.5 (MR4.5) - CML-CP No Prior Dasatinib Participants Up to 36 Months 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
Duration of Molecular Response 4.5 (MR4.5) - CML-CP Prior Dasatinib Participants Up to 36 Months 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
Duration of Molecular Response 4.5 (MR4.5) - CML-AP Participants Up to 36 Months 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
Trial Locations
- Locations (13)
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
QEII Health Sciences Centre-VG Site
🇨🇦Halifax, Nova Scotia, Canada
Campus Virchow Klinikum Der Charite
🇩🇪Berlin, Germany
Universitaetsklinikum Bonn
🇩🇪Bonn, Germany
Universitaetsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Local Institution
🇪🇸Valencia, Spain
Ut Southwestern Medical Center At Dallas
🇺🇸Dallas, Texas, United States
Universitaetsklinik Frankfurt
🇩🇪Frankfurt am Main, Germany
Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Dana Farber Cancer Institute.
🇺🇸Boston, Massachusetts, United States
Froedtert Hospital & Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
The University Of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States