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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 15, 2016
Last verified: September 2016

May 3, 2012
September 15, 2016
June 2012
October 2018   (final data collection date for primary outcome measure)
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 ]
Safety and tolerability of BMS-936558 as measured by the occurrence of AEs, SAEs, deaths, hematologic laboratory abnormalities, serum chemistry laboratory abnormalities, and changes in blood pressure and heart rate measurements [ Time Frame: Up to 100 days after the last treatment (expected to be no more than 225 weeks) ] [ Designated as safety issue: Yes ]
  • AEs = adverse events
  • SAEs = serious adverse events
Complete list of historical versions of study NCT01592370 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Maximum observed serum concentration (Cmax) of BMS-936558 [ 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) [Cmin] of BMS-936558 [ Time Frame: 7 time points up to 20 weeks ] [ Designated as safety issue: No ]
  • Time of maximum observed serum concentration (Tmax) of BMS-936558 [ 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 BMS-936558 [ Time Frame: 7 time points up to 20 weeks ] [ Designated as safety issue: No ]
  • Antitumor Activity of BMS-936558 as measured by Best Overall Response (BOR) [ Time Frame: Baseline (within 28 days of treatment), Week 4, Week 8, Week 16, Week 24, and every 16 weeks thereafter until confirmed disease progression assessed 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
  • Antitumor Activity of BMS-936558 as measured by Objective Response Rate (ORR) [ Time Frame: Baseline (within 28 days of treatment), Week 4, Week 8, Week 16, Week 24, and every 16 weeks thereafter until confirmed disease progression assessed up to Week 156 ] [ Designated as safety issue: No ]
    ORR is defined as the proportion of subjects whose BOR is either partial response (PR) or complete response (CR) divided by the number of treated subjects (or response-evaluable subjects)
  • Antitumor Activity of BMS-936558 as measured by duration of Objective Response [ Time Frame: Baseline (within 28 days of treatment), Week 4, Week 8, Week 16, Week 24, and every 16 weeks thereafter until confirmed disease progression assessed up to Week 156 ] [ Designated as safety issue: No ]
    The duration of response is defined as the time when the measurement criteria are first met for PR or CR (whichever is reported first) until the date of documented disease progression or death. For subjects who neither progress nor die, the duration of response will be censored at the date of their last disease assessment
  • Antitumor Activity of BMS-936558 as measured by Progression Free Survival Rate (PFSR) [ Time Frame: Baseline (within 28 days of treatment), Week 4, Week 8, Week 16, Week 24, and every 16 weeks thereafter until confirmed disease progression assessed up to Week 156 ] [ Designated as safety issue: No ]
    The PFSR is defined as the probability of a subject remaining progression free or surviving to time t, where t = 8, 16 and 24 weeks. 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
  • Immunogenicity of BMS-936558 as measured by the frequency of subjects with an increase in anti-drug antibody levels from baseline [ Time Frame: Baseline (within 28 days of treatment), week 4, week 6, week 12, week 20, and at follow-up (35 ± 7 days after last treatment and 90-120 days since last treatment) ] [ Designated as safety issue: Yes ]
  • PD-L1 expression levels [ Time Frame: Baseline (within 28 days of treatment) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety Study of Nivolumab by Itself or in Combination in Patients With Lymphoma or Multiple Myeloma
Multiple Phase 1 Safety 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 with Nivolumab by itself or in combination in patients with relapsed/ refractory lymphoma or multiple myeloma.
Not Provided
Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Non-Hodgkin's Lymphoma
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Biological: Nivolumab
    Other Names:
    • BMS-936558
    • Opdivo
  • Biological: Ipilimumab
    Other Names:
    • Yervoy
    • BMS-734016
    • MDX010
  • Biological: Lirilumab
    Other Name: BMS-986015
  • Biological: Daratumumab
    Other Name: Darzalex
  • Drug: Pomalidomide
    Other Name: Pomalyst
  • Drug: Dexamethasone
    Other Name: Intensol
  • Experimental: Arm 1: Cohort 1-Nivolumab monotherapy (Dose Escalation)

    Nivolumab solution intravenously as specified

    Enrollment is closed for Arm 1

    Non-randomized

    Intervention: Biological: Nivolumab
  • 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

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
    • Biological: Lirilumab
  • Experimental: Daratumumab

    Experimental: Arm 3: Nivolumab and Daratumumab

    Randomized

    Interventions:
    • Biological: Nivolumab
    • Biological: Daratumumab
  • Experimental: Nivolumab, Daratumumab, Pomalidomide, Dexamethasone
    Randomized
    Interventions:
    • Biological: Nivolumab
    • Biological: Daratumumab
    • Drug: Pomalidomide
    • Drug: Dexamethasone
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
375
March 2020
October 2018   (final data collection date for primary outcome measure)

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

Both
18 Years and older   (Adult, Senior)
No
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 #.
United States
 
NCT01592370
CA209-039
No
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP