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An Investigational Immuno-Therapy Study to Determine the Safety and Effectiveness of Nivolumab and Daratumumab in Patients With Multiple Myeloma

NCT01592370

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
NivolumabBMS-936558, OpdivoNivolumab monotherapy (Dose Escalation)
IpilimumabYervoy, BMS-734016, MDX010Nivolumab + Ipilimumab
LirilumabBMS-986015Nivolumab + Lirilumab
DaratumumabDarzalexNivo + Dara + Pom + Dexa vs. Nivo + Dara
PomalidomidePomalystNivo + Dara + Pom + Dexa vs. Nivo + Dara
DexamethasoneIntensolNivo + 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

NameTypeDescriptionInterventions
Nivolumab monotherapy (Dose Escalation)ExperimentalNivolumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort
  • Nivolumab
Nivolumab + IpilimumabExperimentalNivolumab and Ipilimumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort
  • Nivolumab
  • Ipilimumab
Nivolumab + LirilumabExperimentalNon-randomized Nivolumab: 3 mg/kg given every 2 weeks Lirilumab: 3 mg/kg given every 4 weeks Enrollment is closed for this cohort
  • Nivolumab
  • Lirilumab
Nivo + Dara + Pom + Dexa vs. Nivo + DaraExperimentalRandomized 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 + DaratumumabExperimentalRandomized 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
  • Nivolumab
  • Daratumumab

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

November 15, 2019