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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hodgkin Lymphoma; Multiple Myeloma; Non-Hodgkin's Lymphoma

Treatments: Biological: Nivolumab; Biological: Lirilumab; Biological: Daratumumab; Biological: Ipilimumab; Drug: Dexamethasone; Drug: Pomalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01592370

2018-001030-17 (EudraCT Number)

CA209-039

Details and patient eligibility

About

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.

Full description

NOTE: Currently, this study is only open to nivolumab+daratumumab vs daratumumab monotherapy in multiple myeloma patients.

Enrollment: 316 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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316 participants in 5 patient groups

Nivolumab monotherapy (Dose Escalation)

Experimental group

Description:

Nivolumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort

Treatment:

Biological: Nivolumab

Nivolumab + Ipilimumab

Experimental group

Description:

Nivolumab and Ipilimumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort

Treatment:

Biological: Ipilimumab

Biological: Nivolumab

Nivolumab + Lirilumab

Experimental group

Description:

Non-randomized Nivolumab: 3 mg/kg given every 2 weeks Lirilumab: 3 mg/kg given every 4 weeks Enrollment is closed for this cohort

Treatment:

Biological: Lirilumab

Biological: Nivolumab

Nivo + Dara + Pom + Dexa vs. Nivo + Dara

Experimental group

Description:

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

Treatment:

Drug: Dexamethasone

Drug: Pomalidomide

Biological: Daratumumab

Biological: Nivolumab

Daratumumab vs. Nivolumab + Daratumumab

Experimental group

Description:

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

Treatment:

Biological: Daratumumab

Biological: Nivolumab