NCT01592370 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2025-10-22

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants That Experienced Drug Related Grade 3-4 AEs

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outcome · POSTED

Number of Participants That Experienced Drug Related Grade 3-4 SAEs

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outcome · POSTED

Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver

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outcome · POSTED

Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Thyroid

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outcome · POSTED

Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology

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outcome · POSTED

Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver

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outcome · POSTED

Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid

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outcome · POSTED

Best Overall Response

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outcome · POSTED

Best Overall Response - Multiple Myeloma Group

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outcome · POSTED

Duration of Response

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outcome · POSTED

Duration of Response - Multiple Myeloma Group

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outcome · POSTED

Progression Free Survival

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outcome · POSTED

Progression Free Survival Rate

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outcome · POSTED

Overall Survival

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outcome · POSTED

Number of Participants With PD-L1 Expression

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outcome · POSTED

Percentage Change From Baseline in the Modified Severity Weighted Assessment Tool (mSWAT) Score

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outcome · POSTED

Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

Objective Response Rate in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

Duration of Response in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

Progression Free Survival in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

Cmax in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

Tmax in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

Cmin in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

AUC (0-T) in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

AUC (TAU) in the Nivolumab + Daratumumab Cohort

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outcome · POSTED

End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Nivolumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort
intervention Names
Biological: Nivolumab
label
Nivolumab monotherapy (Dose Escalation)
type
EXPERIMENTAL
description
Nivolumab and Ipilimumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort
intervention Names
Biological: Nivolumab
Biological: Ipilimumab
label
Nivolumab + Ipilimumab
type
EXPERIMENTAL
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
intervention Names
Biological: Nivolumab
Biological: Lirilumab
label
Nivolumab + Lirilumab
type
EXPERIMENTAL
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
intervention Names
Biological: Nivolumab
Biological: Daratumumab
Drug: Pomalidomide
Drug: Dexamethasone
label
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
type
EXPERIMENTAL
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
intervention Names
Biological: Nivolumab
Biological: Daratumumab
label
Daratumumab vs. Nivolumab + Daratumumab
type
EXPERIMENTAL

interventions

arm Group Labels
Daratumumab vs. Nivolumab + Daratumumab
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
Nivolumab + Ipilimumab
Nivolumab + Lirilumab
Nivolumab monotherapy (Dose Escalation)
description
Administered by intravenous (IV) infusion
name
Nivolumab
other Names
BMS-936558
Opdivo
type
BIOLOGICAL
arm Group Labels
Nivolumab + Ipilimumab
description
Administered by IV infusion
name
Ipilimumab
other Names
Yervoy
BMS-734016
MDX010
type
BIOLOGICAL
arm Group Labels
Nivolumab + Lirilumab
description
Administered by IV infusion
name
Lirilumab
other Names
BMS-986015
type
BIOLOGICAL
arm Group Labels
Daratumumab vs. Nivolumab + Daratumumab
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
description
Administered by IV infusion
name
Daratumumab
other Names
Darzalex
type
BIOLOGICAL
arm Group Labels
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
description
Administered PO
name
Pomalidomide
other Names
Pomalyst
type
DRUG
arm Group Labels
Nivo + Dara + Pom + Dexa vs. Nivo + Dara
description
Administered PO and by IV infusion
name
Dexamethasone
other Names
Intensol
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 320
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug.
measure
Number of Participants That Experienced Drug Related Grade 3-4 AEs
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
description
Number and percent of participants that experienced drug related Grade 3-4 SAEs occurring up to 100 days after the last dose of study drug.
measure
Number of Participants That Experienced Drug Related Grade 3-4 SAEs
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
description
Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug.
measure
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Thyroid
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
measure
Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort
time Frame
approximately up to 4 years
measure
Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort
time Frame
approximately up to 4 years
measure
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology
time Frame
approximately up to 4 years
measure
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver
time Frame
approximately up to 4 years
measure
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid
time Frame
approximately up to 4 years

secondary Outcomes

description
the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. Measured in Complete Response and Partial Response
measure
Best Overall Response
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
description
the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy.
measure
Best Overall Response - Multiple Myeloma Group
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
description
the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. Measured in Complete Remission and Partial Remission
measure
Duration of Response
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to approximately 37 months Nivo Liri: approximately up to 4 years 1 month
description
the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. Measured in Complete Response and Partial Response
measure
Duration of Response - Multiple Myeloma Group
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
description
Progression free survival (PFS) is defined as the time between date of randomization and date of progression or death, whichever occurs first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Subjects who did not progress or die were censored on the date of their last efficacy assessment.
measure
Progression Free Survival
time Frame
From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months)
description
The percentage of participants remaining progression free at the specified timepoints (up to 48 Months)
measure
Progression Free Survival Rate
time Frame
From randomization to the specified timepoints (up to 48 months)
description
The percentage of participants remaining alive. Median values are computed using Kaplan-Meier method
measure
Overall Survival
time Frame
Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to3 years Nivo Liri: approximately up to 4 years 1 month
description
Number of Participants with PD-L1 expression in the following categories * baseline PD-L1 expression ≥ 1% * baseline PD-L1 expression \< 1% * without PD-L1 quantifiable at baseline
measure
Number of Participants With PD-L1 Expression
time Frame
At baseline (prior to start of study treatment)
description
mSWAT is a scoring technique involving the direct assessment of the percentage of body-surface-area (BSA) affected by skin lesions. There are 12 body regions (each one assigned a different percentage of BSA). For each body region, the assigned BSA percentage is multiplied by a factor weighing the type and severity of lesion observed (patch= x1, plaque = x2, tumor= x4). The sum of the individual body region sub-scores is then summed to generate the final mSWAT score, which ranges from 0 (best outcome) to 400 (worst outcome).
measure
Percentage Change From Baseline in the Modified Severity Weighted Assessment Tool (mSWAT) Score
time Frame
From baseline (last measurement before start of study treatment) to last available measurement after start of study treatment (88 weeks for Nivo mono, 93 weeks for nivo+ipi, 25 weeks for nivo+liri)
description
Time to MRD Negativity status in specific NGS and NGF sensitivity levels
measure
Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort
time Frame
approximately up to 4 years
measure
Objective Response Rate in the Nivolumab + Daratumumab Cohort
time Frame
approximately up to 4 years
measure
Duration of Response in the Nivolumab + Daratumumab Cohort
time Frame
approximately up to 4 years

Full study description

brief Summary: 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.

Source references

references

citation
Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, Millenson MM, Cohen AD, Schuster SJ, Lebovic D, Dhodapkar M, Avigan D, Chapuy B, Ligon AH, Freeman GJ, Rodig SJ, Cattry D, Zhu L, Grosso JF, Bradley Garelik MB, Shipp MA, Borrello I, Timmerman J. Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol. 2016 Aug 10;34(23):2698-704. doi: 10.1200/JCO.2015.65.9789. Epub 2016 Jun 6.
pmid
27269947
type
DERIVED
citation
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015 Jan 22;372(4):311-9. doi: 10.1056/NEJMoa1411087. Epub 2014 Dec 6.
pmid
25482239
type
DERIVED