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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
Recruitment Status : Recruiting
First Posted : May 7, 2012
Last Update Posted : June 19, 2018
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
Bristol-Myers Squibb

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

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 375 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 : June 27, 2012
Estimated Primary Completion Date : June 14, 2020
Estimated Study Completion Date : June 15, 2020


Arm Intervention/treatment
Experimental: Nivolumab monotherapy (Dose Escalation)

Nivolumab solution intravenously as specified

Enrollment is closed for this arm

Non-randomized

Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo

Experimental: Nivolumab + Ipilimumab

Nivolumab and Ipilimumab solution intravenously as specified

Non-randomized

Enrollment is closed for this arm

Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo

Biological: Ipilimumab
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Experimental: Nivolumab + Lirilumab

Non-randomized

Enrollment is closed for this arm

Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo

Biological: Lirilumab
Other Name: BMS-986015

Biological: Daratumumab
Other Name: Darzalex

Experimental: Nivo + Dara + Pom + Dexa vs. Nivo + Dara

Randomized

Enrollment is closed this arm

Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo

Biological: Daratumumab
Other Name: Darzalex

Drug: Pomalidomide
Other Name: Pomalyst

Drug: Dexamethasone
Other Name: Intensol

Experimental: Daratumumab vs. Nivolumab + Daratumumab
Randomized
Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo

Biological: Daratumumab
Other Name: Darzalex




Primary Outcome Measures :
  1. Safety and tolerability of Nivolumab alone and in combination as measured by incidence of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities, and laboratory test abnormalities [ Time Frame: Up to 100 days after the last dose of study (expected to be no more than 225 weeks) ]

Secondary Outcome Measures :
  1. Maximum observed serum concentration (Cmax) [ Time Frame: 7 time points up to 20 weeks ]
  2. Serum concentration achieved at the end of dosing interval (trough concentration, all participants) [Cmin] [ Time Frame: 7 time points up to 20 weeks ]
  3. Time of maximum observed serum concentration (Tmax) [ Time Frame: 7 time points up to 20 weeks ]
  4. Area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration [AUC(0-T)] [ Time Frame: 7 time points up to 20 weeks ]
  5. Area under the concentration-time curve in one dosing interval [AUC(TAU)] [ Time Frame: 7 time points up to 20 weeks ]
  6. Serum concentration achieved at the end of study drug infusion (Ceoinf) [ Time Frame: 7 time points up to 20 weeks ]
  7. Best Overall Response (BOR) [ Time Frame: Baseline (within 28 days of treatment), until disease progression in patients, up to week 156 ]
    BOR is defined as the best response designation over the study as a whole, recorded between the date of first dose and the last tumor assessment prior to subsequent therapy

  8. Objective Response Rate (ORR) [ Time Frame: Baseline up to week 156 ]
    ORR is defined as the proportion of patients whose BOR is either partial response (PR) or complete response (CR) divided by the number of treated patients

  9. Duration of Objective Response [ Time Frame: Baseline until disease progression in patients with multiple myeloma receiving nivolumab in combination with daratumumab, up to week 156 ]
    Duration of response is defined as the time when the measurement criteria are first met for objective response until the date of documented disease progression or death. For patients who neither progress nor die, the duration of response will be censored at the date of their last disease assessment

  10. Progression Free Survival Rate (PFSR) [ Time Frame: Baseline up to week 156 ]
    Progression free survival (PFS) is defined as the time between date of first dose of study therapy and date of progression or death, whichever occurs first

  11. Modified Severity Weighted Assessment Tool (mSWAT) for patients with cutaneous T cell lymphoma [ Time Frame: Baseline up to week 156 ]
  12. Immunogenicity as measured by the anti-drug antibody (ADA) status both at sample level and at patient level [ Time Frame: Baseline, 6 timepoints up to 120 days after the last dose of study drug ]
  13. Minimal Residual Disease (MRD) in patients with multiple myeloma receiving nivolumab in combination with daratumumab [ Time Frame: Up to 41 months ]
  14. PD-L1 expression [ Time Frame: up to 20 weeks ]


Information from the National Library of Medicine

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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


Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 36 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Janssen, LP
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01592370     History of Changes
Other Study ID Numbers: CA209-039
First Posted: May 7, 2012    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Non-Hodgkin
Hodgkin Disease
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
Pomalidomide
Daratumumab
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids