Description:
The purpose of this study is to determine the side effects of treatment of the combination of
nivolumab and daratumumab in participants with relapsed/refractory multiple myeloma.
Title
- Brief Title: An Investigational Immuno-Therapy Study to Determine the Safety and Effectiveness of Nivolumab and Daratumumab in Patients With Multiple Myeloma
- Official Title: Multiple Phase 1/2 Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies
Clinical Trial IDs
- ORG STUDY ID:
CA209-039
- SECONDARY ID:
2018-001030-17
- NCT ID:
NCT01592370
Conditions
- Non-Hodgkin's Lymphoma
- Hodgkin Lymphoma
- Multiple Myeloma
Interventions
| Drug | Synonyms | Arms |
|---|
| Nivolumab | BMS-936558, Opdivo | Daratumumab vs. Nivolumab + Daratumumab |
| Ipilimumab | Yervoy, BMS-734016, MDX010 | Nivolumab + Ipilimumab |
| Lirilumab | BMS-986015 | Nivolumab + Lirilumab |
| Daratumumab | Darzalex | Daratumumab vs. Nivolumab + Daratumumab |
| Pomalidomide | Pomalyst | Nivo + Dara + Pom + Dexa vs. Nivo + Dara |
| Dexamethasone | Intensol | Nivo + Dara + Pom + Dexa vs. Nivo + Dara |
Purpose
The purpose of this study is to determine the side effects of treatment of the combination of
nivolumab and daratumumab in participants with relapsed/refractory multiple myeloma.
Detailed Description
NOTE: Currently, this study is only open to nivolumab+daratumumab vs daratumumab monotherapy
in multiple myeloma patients.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Nivolumab monotherapy (Dose Escalation) | Experimental | Nivolumab solution intravenously as specified
Non-randomized
Enrollment is closed for this cohort | |
| Nivolumab + Ipilimumab | Experimental | Nivolumab and Ipilimumab solution intravenously as specified
Non-randomized
Enrollment is closed for this cohort | |
| Nivolumab + Lirilumab | Experimental | Non-randomized
Nivolumab: 3 mg/kg given every 2 weeks Lirilumab: 3 mg/kg given every 4 weeks
Enrollment is closed for this cohort | |
| Nivo + Dara + Pom + Dexa vs. Nivo + Dara | Experimental | Randomized
Nivolumab:
Cycle 1: 240 mg Day 15 Cycle 2-6: 240 mg Days 1, 15 Cycle 7 & beyond: 480 mg Day 1
Daratumumab:
Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 & beyond: 16 mg/kg Day 1
Pomalidomide:
4 mg po (by mouth) daily on Days 1 - 21 of each 28-day cycle
Dexamethasone:
Weeks without daratumumab dosing:
40 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants ≤ 75 years old
20 mg po daily (Days 1, 8, 15, 22) of each 28-day cycle for participants > 75 years old
Weeks with daratumumab dosing:
20 mg iv before the daratumumab infusion and 20 mg po after the daratumumab infusion in participants ≤ 75 years old
16 mg iv before the daratumumab infusion and 4 mg po after the daratumumab infusion in participants > 75 years old
Enrollment is closed for this cohort | - Nivolumab
- Daratumumab
- Pomalidomide
- Dexamethasone
|
| Daratumumab vs. Nivolumab + Daratumumab | Experimental | Randomized
Nivolumab:
Cycle 1: 240 mg Day 15 Cycle 2 & beyond: 480 mg Day 1
Daratumumab:
Cycle 1-2: 16 mg/kg Days 1, 8, 15, 22 Cycle 3-6: 16 mg/kg Days 1, 15 Cycle 7 & beyond: 16 mg/kg Day 1 | |
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com
Inclusion Criteria:
- Have received at least 3 prior lines of therapy, including a proteasome inhibitor [PI]
and an immunomodulatory agent [IMiD] OR have disease that is double refractory to a PI
and IMiD
- More than 12 weeks post-transplant of your own blood forming stem cells (autologous
transplant)
- Have detectable disease measured by a specific protein in your blood and/or urine
- Must consent to bone marrow aspirate or biopsy.
Exclusion Criteria:
- Solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell
dyscrasia, or monoclonal gammopathy of undetermined significance (MGUS), smoldering
multiple myeloma (SMM), primary amyloidosis, Waldenstrom's macroglobulinemia, POEMS
syndrome or active plasma cell leukemia
- Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti CTLA 4, or
anti-CD38 antibody, or allogeneic stem cell transplantation
- Seropositive for human immunodeficiency virus (HIV), Hepatitis B surface antigen or
Hepatitis C antibody positive (except if HCV-RNA negative), or history of active
chronic hepatitis B or C
- History of central nervous system involvement or symptoms suggestive of central
nervous system involvement by multiple myeloma
Other protocol defined inclusion/exclusion criteria could apply
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number and percent of subjects that experience drug-related grade 3-4 adverse events (AEs) occurring up to 100 days after the last dose of study drug |
| Time Frame: | On a continuous basis up to 100 days after the last dose of study drug |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Minimal Residual Disease (MRD) in the Nivolumab/Daratumumab Cohorts in patients with multiple myeloma receiving the assigned treatment regimen |
| Time Frame: | Up to 41 months |
| Safety Issue: | |
| Description: | |
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | Baseline up to week 156 |
| Safety Issue: | |
| Description: | |
| Measure: | Best Overall Response (BOR) |
| Time Frame: | Baseline (within 28 days of treatment), until disease progression in patients, up to week 156 |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Objective Response |
| Time Frame: | Baseline until disease progression in patients with multiple myeloma receiving the assigned treatment regimen, up to week 156 |
| Safety Issue: | |
| Description: | |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | Baseline up to week 156 |
| Safety Issue: | |
| Description: | |
| Measure: | Maximum observed serum concentration (Cmax) |
| Time Frame: | 7 time points up to 20 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | Time of maximum observed serum concentration (Tmax) |
| Time Frame: | 7 time points up to 20 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | Serum concentration achieved at the end of dosing interval (trough concentration, all participants) [Cmin] |
| Time Frame: | 7 time points up to 20 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | Area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration [AUC(0-T)] |
| Time Frame: | 7 time points up to 20 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | Area under the concentration-time curve in one dosing interval [AUC(TAU)] |
| Time Frame: | 7 time points up to 20 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | Serum concentration achieved at the end of study drug infusion (Ceoinf) |
| Time Frame: | 7 time points up to 20 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | Immunogenicity as measured by the anti-drug antibody (ADA) status both at sample level and at patient level |
| Time Frame: | Baseline, 6 timepoints up to 120 days after the last dose of study drug |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Bristol-Myers Squibb |
Last Updated
June 18, 2021
