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Safety Study of Nivolumab by Itself or in Combination in Patients With Lymphoma or Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01592370
First received: May 3, 2012
Last updated: September 23, 2016
Last verified: September 2016
  Purpose
The purpose of this study is to determine the side effects of treatment with Nivolumab by itself or in combination in patients with relapsed/ refractory lymphoma or multiple myeloma.

Condition Intervention Phase
Non-Hodgkin's Lymphoma
Hodgkin Lymphoma
Multiple Myeloma
Biological: Nivolumab
Biological: Ipilimumab
Biological: Lirilumab
Biological: Daratumumab
Drug: Pomalidomide
Drug: Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multiple Phase 1 Safety Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum observed serum concentration (Cmax) of Nivolumab, Ipilimumab and Lirilumab [ Time Frame: 7 time points up to 20 weeks ] [ Designated as safety issue: No ]
  • Serum concentration achieved at the end of dosing interval (trough concentration, all patients) [Cmin] of Nivolumab, Ipilimumab and Lirilumab [ Time Frame: 7 time points up to 20 weeks ] [ Designated as safety issue: No ]
  • Time of maximum observed serum concentration (Tmax) of Nivolumab, Ipilimumab and Lirilumab [ Time Frame: 7 time points up to 20 weeks ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration [AUC(0-T)] of Nivolumab, Ipilimumab and Lirilumab [ Time Frame: 7 time points up to 20 weeks ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of Nivolumab, Ipilimumab and Lirilumab [ Time Frame: 7 time points up to 20 weeks ] [ Designated as safety issue: No ]
  • Serum concentration achieved at the end of study drug infusion (Ceoinf) of Nivolumab, Ipilimumab and Lirilumab [ Time Frame: 7 time points up to 20 weeks ] [ Designated as safety issue: No ]
  • Best Overall Response (BOR) [ Time Frame: Baseline (within 28 days of treatment), until disease progression in patients, up to week 156 ] [ Designated as safety issue: No ]
    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

  • Objective Response Rate (ORR) [ Time Frame: Baseline up to week 156 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    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

  • Progression Free Survival Rate (PFSR) [ Time Frame: Baseline up to week 156 ] [ Designated as safety issue: No ]
    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

  • Modified Severity Weighted Assessment Tool (mSWAT) for patients with cutaneous T cell lymphoma [ Time Frame: Baseline up to week 156 ] [ Designated as safety issue: No ]
  • Immunogenicity of Nivolumab, Ipilimumab and Lirilumab 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 ] [ Designated as safety issue: Yes ]
  • Minimal Residual Disease (MRD) for in patients with multiple myeloma receiving nivolumab in combination with daratumumab [ Time Frame: Up to 41 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 375
Study Start Date: June 2012
Estimated Study Completion Date: March 2020
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Cohort 1-Nivolumab monotherapy (Dose Escalation)

Nivolumab solution intravenously as specified

Enrollment is closed for Arm 1

Non-randomized

Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo
Experimental: Arm 2: Cohort 1-Nivolumab + Ipilimumab / Lirilumab

Nivolumab and Ipilimumab or Lirilumab solution intravenously as specified

Enrollment is closed for Arm 2

Non-randomized

Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo
Biological: Ipilimumab
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Biological: Lirilumab
Other Name: BMS-986015
Experimental: Daratumumab

Experimental: Arm 3: Nivolumab and Daratumumab

Randomized

Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo
Biological: Daratumumab
Other Name: Darzalex
Experimental: Nivolumab, Daratumumab, Pomalidomide, Dexamethasone
Randomized
Biological: Nivolumab
Other Names:
  • BMS-936558
  • Opdivo
Biological: Daratumumab
Other Name: Darzalex
Drug: Pomalidomide
Other Name: Pomalyst
Drug: Dexamethasone
Other Name: Intensol

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Relapsed or Unresponsive to prior treatment for multiple myeloma
  • ≥2 courses of therapy, including at least 2 consecutive cycles of each immunomodulatory agent (IMiD) and a proteasome inhibitor (PI) alone or in combination
  • 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 a 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), amyloidosis, Waldenstrom's macroglobulinemia, POEMS syndrome or active plasma cell leukemia
  • No prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti CTLA 4, or anti-CD38 antibody, or with pomalidomide, 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

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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 #.

Locations
United States, California
Ucla Department Of Medicine Active, not recruiting
Los Angeles, California, United States, 90095
United States, Connecticut
Yale University School Of Medicine Completed
New Haven, Connecticut, United States, 06520
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Ivan Borrello, Site 003    410-614-0482      
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Philippe Armand, Site 0015    617-667-3064      
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Philippe Armand, Site 009    617-582-8437      
United States, Michigan
University Of Michigan Health System Completed
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Stephen Ansell, Site 002    855-776-0015      
United States, New Jersey
John Theurer Cancer Center Active, not recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan Kettering Cancer Ctr Recruiting
New York, New York, United States, 10065
Contact: Alexander Lesokhin, Site 001    646-888-3359      
United States, Oregon
Ohsu Center For Hematologic Malignancies Recruiting
Portland, Oregon, United States, 97239
Contact: Emma Scott, Site 006    503-494-4603      
United States, Pennsylvania
Abramson Cancer Center Of The University Of Pennsylvania Completed
Philadelphia, Pennsylvania, United States, 19104
Fox Chase Cancer Center Active, not recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, Utah
Huntsman Cancer Institute At The Univ. Of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Ahmad Halwani, Site 005    801-213-4230      
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

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 
Study First Received: May 3, 2012
Last Updated: September 23, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
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 acetate
Dexamethasone
Dexamethasone 21-phosphate
Nivolumab
Pomalidomide
Daratumumab
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 28, 2016