An Investigational Immuno-Therapy Study to Determine the Safety and Effectiveness of Nivolumab and Daratumumab in Patients With Multiple Myeloma
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| ClinicalTrials.gov Identifier: NCT01592370 |
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Recruitment Status :
Active, not recruiting
First Posted : May 7, 2012
Results First Posted : February 17, 2022
Last Update Posted : April 28, 2023
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Sponsor:
Bristol-Myers Squibb
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
Bristol-Myers Squibb
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-Hodgkin's Lymphoma Hodgkin Lymphoma Multiple Myeloma | Biological: Nivolumab Biological: Ipilimumab Biological: Lirilumab Biological: Daratumumab Drug: Pomalidomide Drug: Dexamethasone | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 316 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Multiple Phase 1/2 Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies |
| Actual Study Start Date : | August 2, 2012 |
| Actual Primary Completion Date : | September 25, 2020 |
| Estimated Study Completion Date : | December 22, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Nivolumab monotherapy (Dose Escalation)
Nivolumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort |
Biological: Nivolumab
Administered by intravenous (IV) infusion
Other Names:
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Experimental: Nivolumab + Ipilimumab
Nivolumab and Ipilimumab solution intravenously as specified Non-randomized Enrollment is closed for this cohort |
Biological: Nivolumab
Administered by intravenous (IV) infusion
Other Names:
Biological: Ipilimumab Administered by IV infusion
Other Names:
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Experimental: Nivolumab + Lirilumab
Non-randomized Nivolumab: 3 mg/kg given every 2 weeks Lirilumab: 3 mg/kg given every 4 weeks Enrollment is closed for this cohort |
Biological: Nivolumab
Administered by intravenous (IV) infusion
Other Names:
Biological: Lirilumab Administered by IV infusion
Other Name: BMS-986015 |
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Experimental: Nivo + Dara + Pom + Dexa vs. Nivo + Dara
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:
Weeks with daratumumab dosing:
Enrollment is closed for this cohort |
Biological: Nivolumab
Administered by intravenous (IV) infusion
Other Names:
Biological: Daratumumab Administered by IV infusion
Other Name: Darzalex Drug: Pomalidomide Administered PO
Other Name: Pomalyst Drug: Dexamethasone Administered PO and by IV infusion
Other Name: Intensol |
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Experimental: Daratumumab vs. Nivolumab + Daratumumab
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 |
Biological: Nivolumab
Administered by intravenous (IV) infusion
Other Names:
Biological: Daratumumab Administered by IV infusion
Other Name: Darzalex |
Primary Outcome Measures :
- 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 ]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.
- 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 ]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.
- 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 ]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.
- 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 ]
- Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]
- Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]
- Number of Participants That Experience Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]
- Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology [ Time Frame: approximately up to 4 years ]
- Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver [ Time Frame: approximately up to 4 years ]
- 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 Outcome Measures :
- 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 ]
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
- 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 ]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.
- 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 ]
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
- 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 ]
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
- Progression Free Survival [ Time Frame: From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months) ]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.
- Progression Free Survival Rate [ Time Frame: From randomization to the specified timepoints (up to 48 months) ]The percentage of participants remaining progression free at the specified timepoints (up to 48 Months)
- 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 ]The percentage of participants remaining alive. Median values are computed using Kaplan-Meier method
- Number of Participants With PD-L1 Expression [ Time Frame: At baseline (prior to start of study treatment) ]
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
- 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) ]
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).
- Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]Time to MRD Negativity status in specific NGS and NGF sensitivity levels
- Objective Response Rate in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]
- Duration of Response in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]
- Progression Free Survival in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]
- Cmax in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]Maximum observed serum concentration
- Tmax in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]Time of maximum observed serum concentration
- Cmin in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]Serum concentration achieved at the end of dosing interval (trough concentration)
- AUC (0-T) in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]Area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration
- AUC (TAU) in the Nivolumab + Daratumumab Cohort [ Time Frame: approximately up to 4 years ]Area under the concentration-time curve in one dosing interval
- End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort [ Time Frame: Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days ]Serum concentration achieved at the end of study drug infusion
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01592370
Locations
Show 43 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Janssen, LP
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Study Documents (Full-Text)
Documents provided by Bristol-Myers Squibb:
Documents provided by Bristol-Myers Squibb:
Study Protocol [PDF] April 23, 2019
Statistical Analysis Plan [PDF] September 8, 2021
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01592370 |
| Other Study ID Numbers: |
CA209-039 2018-001030-17 ( EudraCT Number ) |
| First Posted: | May 7, 2012 Key Record Dates |
| Results First Posted: | February 17, 2022 |
| Last Update Posted: | April 28, 2023 |
| Last Verified: | April 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Lymphoma Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases |
Hemorrhagic Disorders Dexamethasone Nivolumab Ipilimumab Daratumumab Pomalidomide Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |