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A Study to Evaluate the Safety, Tolerability, and Efficacy of Relatlimab in Relapsed or Refractory B-Cell Malignancies

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ClinicalTrials.gov Identifier: NCT02061761
Recruitment Status : Active, not recruiting
First Posted : February 13, 2014
Last Update Posted : October 1, 2021
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The primary objective of this study is to characterize the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of relatlimab administered alone or in combination with nivolumab to subjects with relapsed or refractory B-cell malignancies. Co-primary objective is to investigate the preliminary efficacy of relatlimab in combination with nivolumab in subjects with relapsed or refractory Hodgkin lymphoma (HL), and relapsed or refractory Diffused Large B Cell lymphoma (DLBCL)

Condition or disease Intervention/treatment Phase
Hematologic Neoplasms Biological: BMS-986016 Biological: BMS-936558 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 107 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (Relatlimab, BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Relapsed or Refractory B-Cell Malignancies
Actual Study Start Date : March 13, 2014
Estimated Primary Completion Date : February 19, 2022
Estimated Study Completion Date : June 4, 2022


Arm Intervention/treatment
Experimental: Part A - relatlimab (Dose escalation) Biological: BMS-986016
Specified Dose on Specified Days
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3), relatlimab

Experimental: Part C - relatlimab + nivolumab (Dose escalation) Biological: BMS-986016
Specified Dose on Specified Days
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3), relatlimab

Biological: BMS-936558
Specified Dose on Specified Days
Other Name: Anti-PD-1 (Anti-Programmed-Death-1), MDX-1106, nivolumab

Experimental: Part B - relatlimab (Cohort expansion) Biological: BMS-986016
Specified Dose on Specified Days
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3), relatlimab

Experimental: Part D - relatlimab + nivolumab (Cohort expansion) Biological: BMS-986016
Specified Dose on Specified Days
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3), relatlimab

Biological: BMS-936558
Specified Dose on Specified Days
Other Name: Anti-PD-1 (Anti-Programmed-Death-1), MDX-1106, nivolumab




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) [ Time Frame: Approximately 28 months ]
  2. Incidence of AEs leading to discontinuation [ Time Frame: Approximately 28 months ]
  3. Incidence of Serious Adverse Events (SAEs) [ Time Frame: Approximately 28 months ]
  4. Incidence of Deaths [ Time Frame: Approximately 28 months ]
  5. Incidence of clinically significant changes in clinical laboratory values: Hematology tests [ Time Frame: Approximately 28 months ]
  6. Incidence of clinically significant changes in clinical laboratory values: Chemistry tests [ Time Frame: Approximately 28 months ]
  7. Incidence of clinically significant changes in clinical laboratory values: Serology tests [ Time Frame: Approximately 28 months ]
  8. Incidence of clinically significant changes in clinical laboratory values: Endocrine panel [ Time Frame: Approximately 28 months ]
  9. Incidence of clinically significant changes in clinical laboratory values: Urinalysis [ Time Frame: Approximately 28 months ]
  10. Incidence of clinically significant changes in clinical laboratory values: Cardiac Troponin [ Time Frame: Approximately 28 months ]
  11. Objective response rate (ORR) in Part D [ Time Frame: Approximately 4 years ]
    Efficacy measured by proportion of treated subjects with a best overall response of complete response/complete remission (CR) or partial response/partial remission (PR)

  12. Duration of Response (DOR) in Part D [ Time Frame: Approximately 4 years ]
    Efficacy measured by the duration of response for all treated subjects with a best overall response of CR or PR


Secondary Outcome Measures :
  1. Maximum observed serum concentration (Cmax) of BMS-986016 administered alone and in combination with Nivolumab [ Time Frame: Approximately 28 months ]
  2. Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  3. Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  4. Concentration at the end of a dosing interval (Ctau) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  5. Average concentration over a dosing interval [AUC(TAU)/tau] (Css,avg) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  6. Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  7. Total body clearance (CLT) of BMS-986016 administered both alone alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  8. Effective elimination half-life that explains the degree of AUC administered alone accumulation observed (T-HALFeff AUC) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  9. Effective elimination half-life that explains the degree of Cmax administered alone accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  10. Accumulation index; ration of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  11. Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  12. Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  13. Degree of fluctuation or fluctuation index ([Cmax - Ctau]/Css,avg) (DF) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
  14. Incidence of ADA to nivolumab and BMS-986016 [ Time Frame: Approximately 28 Months ]


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:

  • Must have histologic or cytologic confirmation of chronic lymphocytic leukemia, Hodgkin lymphoma, Non-Hodgkin lymphoma, or Multiple Myeloma and have relapsed following prior treatment or been refractory to prior treatment
  • Must have progressed or been refractory to, at least one prior standard therapy, including radiation, immunomodulatory agents (eg, lenalidomide), immunotherapy, cytotoxic chemotherapy, and select antibody (anti-CD20, alemtuzumab, or anti-CD30) therapy.
  • Must be more than 100 days post autologous transplant

Exclusion Criteria:

  • Known or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease (controlled CNS metastases are allowed)
  • Known or suspected autoimmune disease
  • History of allergy to anti-PD-1 or anti-PD-L1 antibody therapy or to other monoclonal antibodies or related compounds or to any of their components

Other protocol-defined inclusion/exclusion criteria 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): NCT02061761


Locations
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United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University School Of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
University of Washington
Seattle, Washington, United States, 98109
Canada, British Columbia
BC Cancer Agency - Vancouver Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02061761    
Other Study ID Numbers: CA224-022
First Posted: February 13, 2014    Key Record Dates
Last Update Posted: October 1, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bristol-Myers Squibb:
Hodgkin lymphoma
non-Hodgkin lymphoma
diffused large B-cell lymphoma
indolent lymphoma
chronic lymphocytic leukemia
relapsed
refractory
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms
Neoplasms by Site
Hematologic Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action