Description:
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.
Title
- Brief Title: A Phase 1B Study to Investigate the Safety and Preliminary Efficacy for the Combination of Dasatinib Plus Nivolumab in Patients With Chronic Myeloid Leukemia
- Official Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
CA180-373
- SECONDARY ID:
2013-002156-33
- NCT ID:
NCT02011945
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Dasatinib | BMS-354825 | Dose Level 1 |
| Nivolumab | BMS-936558 | Dose Level 1 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| dasatinib Only | Experimental | dasatinib 100 mg QD(CP) or 140 mg QD (AP) | |
| Dose Level 1 | Experimental | Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) | |
| Dose Level 2 | Experimental | Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) | |
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com.
Inclusion Criteria:
- 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
Exclusion Criteria:
- Blast phase CML
- Known Abl-kinase mutation resistant to Dasatinib (e.g. T315I or T315A)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of Dose Limiting Toxicities (DLT) |
| Time Frame: | Week 3 to week 6 |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants |
| Time Frame: | upto 36 Months |
| Safety Issue: | |
| 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 Frame: | upto 36 Months |
| Safety Issue: | |
| 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 Frame: | upto 36 Months |
| Safety Issue: | |
| 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 Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants |
| Time Frame: | upto 36 Months |
| Safety Issue: | |
| 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 Frame: | upto 36 Months |
| Safety Issue: | |
| 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 Frame: | upto 36 Months |
| Safety Issue: | |
| 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: | Time to Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants |
| Time Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 Frame: | Up to 36 Months |
| Safety Issue: | |
| 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: | Duration of Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants |
| Time Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 Frame: | Up to 36 Months |
| Safety Issue: | |
| 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: | Time to Molecular Response 4.5(MR4.5) - CML-CP No Prior Dasatinib Participants |
| Time Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 Frame: | Up to 36 Months |
| Safety Issue: | |
| 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: | Duration of Molecular Response 4.5 (MR4.5) - CML-CP No Prior Dasatinib Participants |
| Time Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 Frame: | Up to 36 Months |
| Safety Issue: | |
| 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 |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Bristol-Myers Squibb |
Last Updated
March 18, 2020
