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



The purpose of this study is to test the effectiveness, safety, and tolerability of an investigational drug called nivolumab. This study will determine the safety in subjects that receive nivolumab when given in combination with daratumumab, or dartartumumab alone in relapsed and/or refractory multiple myeloma.

Nivolumab is an antibody (a type of human protein) that is being tested to see if it will allow the body’s immune system to work against tumor cells. It has been approved by the FDA for the treatment of metastatic melanoma (a type of skin cancer), and specific types of previously treated advanced lung and kidney cancers.

Daratumumab is a human CD38-directed monoclonal antibody and is approved as monotherapy for third line treatment of MM patients who failed prior therapy.

Another purpose of this study is to evaluate the low-level disease in your blood, urine and bone marrow (minimal residual disease), percentage of patients whose cancer shrinks or disappears after treatment (overall response rate), how long your body responds (duration of response), how long you stay free of disease (progression free survival), your bodies immune response to nivolumab, and how nivolumab works in body.

BMS hopes to use the data from this study together with data from other clinical studies using these investigational drugs to determine the most effective combination of nivolumab for further study.

Approximate Number of Participants and the Expected Duration of Your Participation in the Study

About 60 subjects are expected for this treatment regimen. Even though you may meet all the criteria for participation, it is possible that you will not be enrolled in this study. If you are enrolled, the duration of your participation will depend on your response to treatment. After completing all study treatments or after you are withdrawn from treatment, you will be asked to continue with follow-up visits to monitor for side effects or potential benefits you may be experiencing from study treatment. Your total participation in this study from the time you have signed the informed consent form through to your last visit may be a maximum of 5 years (depending on how your cancer responds to treatment and how well you tolerate the treatment).

Study Treatments

During the study, the Sponsor wants to find out what effects, good or bad, the study drugs may have on you. You will be randomized (assigned to a treatment group by chance) to 1 of 2 treatment groups. That means you have 66.6% chance you will receive nivolumab in combination with daratumumab and a 33.3% chance you will receive daratumumab alone. You will be assigned to a group once you qualify for the study, and you will be told which group you have been assigned to. There are no placebos (sugar pills) used in this trial. A treatment cycle is defined as 28 days (4 weeks).

How will the study treatment be administered?

Nivolumab in combination with Daratumumab regimen: (40 patients)

Each cycle is 28 days long

Nivolumab: drug is a solution given through a vein and takes about a half hour (30 minutes) with a total dose of 240 mg given on Day 15, in Cycle 1, then 480 mg given every 28 days from Cycle 2 Day 1onward (dose is not based on your body weight).

  • Cycle 1: 240 mg iv Day 15
  • Cycle 2 & beyond: 480 mg iv Day 1

Daratumumab: drug is a solution given through a vein and takes about 7-9 hours for the first dose and about 3-4 hours all other doses. Daratumumab is given at a dose of 16 mg/kg (dose is based on your body weight) every week for the first 2 cycles, then every 2 weeks for the following 4 cycles, and then every 4 weeks from Cycle 7 onward.

  • Cycle 1-2: Days 1, 8, 15, 22
  • Cycle 3-6: Days 1, 15
  • Cycle 7 & beyond: Day 1

Daratumumab - Mono regimen: (20 Patients)

Each cycle is 28 days long

Daratumumab: drug is a solution given through a vein and takes about 7-9 hours for the first dose and about 3-4 hours all other doses. Daratumumab is given at a dose of 16 mg/kg (dose is based on your body weight) every week for the first 2 cycles, then every 2 weeks for the following 4 cycles, and then every 4 weeks from Cycle 7 onward.

  • Cycle 1-2: Days 1, 8, 15, 22
  • Cycle 3-6: Days 1, 15
  • Cycle 7 & beyond: Day 1

Post-Study Access to Therapy to be offered:

If you complete the study and your study doctor has determined that you have benefited from the study medication, you may be eligible to continue to receive the study medication up to a maximum of 24 months. In order to continue receiving study medication, you may be required to enroll into another study, stay in the current study (through a study extension), or enroll into a program that is not part of a clinical study.

There are three periods to the study: screening, treatment, and follow-up periods.

  • Screening: The Screening Period of the study can take up to 28 days to complete. This period may include more than one study visit for various procedures.
  • Treatment (28 day dosing cycles): At each in office treatment day you receive intervenous study medication, you will also receive a brief physical exam, blood tests (these may be taken up to 3 days prior) and assessment of side effects you may be having.

If you experience any changes in your body or develop any new or worsening side effects during or after the infusion you should inform the study doctor or nurse immediately.

  • Follow-up: When you stop or complete study treatments you will begin the last part of the study, the follow-up period. During this period your study doctor will continue to assess your health condition.
    • Safety Followup: Follow up visit 1 approximately 30 days after last treatment and Follow up visit 2 is 100 days after last treatment. These two follow up visits will be at your doctor’s office.
    • Survival Followup: In addition to the standard follow up period, after you discontinue from study treatment or discontinue from the safety follow-up portion of the study, you will be followed every 12 weeks, either in person or by telephone, until completion of the study.
    • If you end treatment for a reason other than your disease getting worse (“disease progression”), you will be asked to be followed every 4 weeks from date of first dose of study drug until disease progression using myeloma labs from blood, and the 24-hour urine collection.
    • If you are unable to return to the study clinic every 4 weeks for testing, your study doctor may send any myeloma test results you have to the sponsor. This information will be collected by the study staff, from your local doctor, and sent to the Sponsor.
SparkCures ID 222
Trial Phase Phase 1/2
Enrollment 60 Patients
Trial Sponsors
  • Bristol-Myers Squibb
NCT Identifier


Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

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

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