Non-Hodgkin's LymphomaPhase 1/2NCT01592370
An Investigational Immuno-Therapy Study to Determine the Safety and Effectiveness of Nivolumab and Daratumumab in Patients With Multiple Myeloma
A Phase 1/2 study testing Nivolumab, Ipilimumab and Lirilumab in people with Non-Hodgkin's Lymphoma and Hodgkin Lymphoma, run by Bristol-Myers Squibb at 43 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Hodgkin Lymphoma, Multiple Myeloma
- What is being tested?
- Nivolumab, Ipilimumab and Lirilumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 43 sitesin 6 countries
- Study dates
- 2 Aug 2012to 9 Jul 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
43 sites in 6 countries.
43 sites in 6 countries
United States32 sites
Local Institution - 0011
Ann Arbor, Michigan, 48109
University Of Michigan Health System
Ann Arbor, Michigan, 48109
Local Institution - 0017
Aurora, Colorado, 80045
Local Institution - 0003
Baltimore, Maryland, 21231
The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Local Institution - 0009
Boston, Massachusetts, 02215
Local Institution - 0015
Boston, Massachusetts, 02215
Local Institution - 0035
Clovis, California, 93611
Local Institution - 0028
Columbus, Ohio, 43210
John Theurer Cancer Center
Hackensack, New Jersey, 07601
Local Institution - 0014
Hackensack, New Jersey, 07601
Local Institution - 0019
Indianapolis, Indiana, 46202
Division Of Hematology & Oncology Ctr. For Health Sciences
Los Angeles, California, 90095
Local Institution - 0012
Los Angeles, California, 90095
Local Institution - 013
New Haven, Connecticut, 06520
Local Institution - 0001
New York, New York, 10065
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Local Institution - 0033
Omaha, Nebraska, 68130
Local Institution - 0023
Orlando, Florida, 32804
Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Local Institution - 0007
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Local Institution - 0004
Philadelphia, Pennsylvania, 19111
Local Institution - 0006
Portland, Oregon, 97239
OHSU Center for Hematologic Malignancies
Portland, Oregon, 97239
Local Institution - 0002
Rochester, Minnesota, 55905
Mayo Clinic
Rochester, Minnesota, 55905
Huntsman Cancer Institute At The Univ. Of Utah
Salt Lake City, Utah, 84112
Local Institution - 0005
Salt Lake City, Utah, 84112
Local Institution - 0037
Skokie, Illinois, 60077
Local Institution - 0018
Westwood, Kansas, 66205
Poland4 sites
Local Institution
Chorzów, 41-500
Local Institution - 0040
Poznan, 61-848
Local Institution - 0049
Warsaw, 02-776
Local Institution - 0042
Wroclaw, 50-367
Belgium3 sites
Local Institution - 0045
Ghent, 9000
Local Institution - 0047
Sint-Niklaas, 9100
Local Institution
Yvoir, B-5530
France2 sites
Local Institution - 0044
Nantes, 44000
Local Institution - 0043
Poitiers, Vienne, 86021
About this study
Official title: Multiple Phase 1/2 Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies
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.
Read the detailed description
NOTE: Currently, this study is only open to nivolumab+daratumumab vs daratumumab monotherapy in multiple myeloma patients.
- Conditions
- Non-Hodgkin's Lymphoma, Hodgkin Lymphoma, Multiple Myeloma
- Being tested
- Nivolumab, Ipilimumab, Lirilumab, Daratumumab, Pomalidomide
- Medical subject headings
- Lymphoma, Non-Hodgkin, Hodgkin Disease, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
Also called BMS-936558, Opdivo
Administered by intravenous (IV) infusion
IpilimumabBiological
Also called Yervoy, BMS-734016, MDX010
Administered by IV infusion
LirilumabBiological
Also called BMS-986015
Administered by IV infusion
DaratumumabBiological
Also called Darzalex
Administered by IV infusion
PomalidomideDrug
Also called Pomalyst
Administered PO
DexamethasoneDrug
Also called Intensol
Administered PO and by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab monotherapy (Dose Escalation) | Experimental | Nivolumab solution intravenously as specified
Non-randomized
Enrollment is closed for this cohort Receives: Biological: Nivolumab |
| Nivolumab + Ipilimumab | Experimental | Nivolumab and Ipilimumab solution intravenously as specified
Non-randomized
Enrollment is closed for this cohort Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Lirilumab |
| 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 Receives: Biological: Nivolumab; Biological: Daratumumab; Drug: Pomalidomide; Drug: 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 Receives: Biological: Nivolumab; Biological: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Experienced Drug Related Grade 3-4 AEs
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.
Measured: 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
Number of Participants That Experienced Drug Related Grade 3-4 SAEs
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.
Measured: 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
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver
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.
Measured: 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
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Thyroid
Measured: 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
Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort
Measured: approximately up to 4 years
Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort
Measured: approximately up to 4 years
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology
Measured: approximately up to 4 years
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver
Measured: approximately up to 4 years
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid
Measured: approximately up to 4 years
Secondary outcomes (19)
Best Overall Response
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
Measured: 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
Best Overall Response - Multiple Myeloma Group
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: 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
Duration of Response
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
Measured: 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
Duration of Response - Multiple Myeloma Group
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
Measured: 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
Progression Free Survival
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.
Measured: From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months)
Progression Free Survival Rate
The percentage of participants remaining progression free at the specified timepoints (up to 48 Months)
Measured: From randomization to the specified timepoints (up to 48 months)
Overall Survival
The percentage of participants remaining alive. Median values are computed using Kaplan-Meier method
Measured: 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
Number of Participants With PD-L1 Expression
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
Measured: At baseline (prior to start of study treatment)
Percentage Change From Baseline in the Modified Severity Weighted Assessment Tool (mSWAT) Score
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).
Measured: 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)
Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort
Time to MRD Negativity status in specific NGS and NGF sensitivity levels
Measured: approximately up to 4 years
Objective Response Rate in the Nivolumab + Daratumumab Cohort
Measured: approximately up to 4 years
Duration of Response in the Nivolumab + Daratumumab Cohort
Measured: approximately up to 4 years
Progression Free Survival in the Nivolumab + Daratumumab Cohort
Measured: approximately up to 4 years
Cmax in the Nivolumab + Daratumumab Cohort
Maximum observed serum concentration
Measured: approximately up to 4 years
Tmax in the Nivolumab + Daratumumab Cohort
Time of maximum observed serum concentration
Measured: approximately up to 4 years
Cmin in the Nivolumab + Daratumumab Cohort
Serum concentration achieved at the end of dosing interval (trough concentration)
Measured: approximately up to 4 years
AUC (0-T) in the Nivolumab + Daratumumab Cohort
Area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration
Measured: approximately up to 4 years
AUC (TAU) in the Nivolumab + Daratumumab Cohort
Area under the concentration-time curve in one dosing interval
Measured: approximately up to 4 years
End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort
Serum concentration achieved at the end of study drug infusion
Measured: Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2012 (estimated)
- Study start2 Aug 2012
- Primary completion25 Sep 2020
- Study completion9 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen, LP
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01592370
- Sponsor's protocol ID
- CA209-039
- Other IDs
- 2018-001030-17, 2018
- Status last verified
- Oct 2025
- First submitted
- 3 May 2012
- Last updated
- 22 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 27269947Ansell 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.
PubMed 25482239