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Safety Study of Anti-LAG-3 in Relapsed or Refractory Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT02061761
Recruitment Status : Recruiting
First Posted : February 13, 2014
Last Update Posted : November 15, 2018
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
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Brief Summary:
The primary objective of this study is to characterize the safety, tolerability and maximum tolerated dose of BMS-986016 administered alone or in combination with Nivolumab to subjects with relapsed hematologic malignancies. Co-primary objective is to investigate the preliminary efficacy of BMS-986016 in combination with nivolumab in subjects with relapsed or refractory Hodgkin lymphoma (HL), and relapsed or refractory Diffuse Large B Cell lymphoma (DLBCL)

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 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 (BMS-986016) in Monoclonal Antibody (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 : February 25, 2014
Estimated Primary Completion Date : March 29, 2019
Estimated Study Completion Date : January 15, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: BMS-986016
BMS-986016 specified dose on specified days
 Biological: BMS-986016
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)
Experimental: BMS-986016 + BMS-936558
BMS-986-016 + BMS-936558 specified dose on specified days
 Biological: BMS-986016
Other Name: Anti-LAG-3 (Anti-Lymphocyte Activation Gene-3)

Biological: BMS-936558
Other Name: Anti-PD-1 (Anti-Programmed-Death-1) ,MDX-1106 , Nivolumab


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of subjects with Adverse Events (AEs) [ Time Frame: Approximately 28 months ]
    Safety measured by incidence

  2. Proportion of subjects with Serious Adverse Events (SAEs) [ Time Frame: Approximately 28 months ]
    Safety measured by incidence

  3. Proportion of Deaths [ Time Frame: Approximately 28 months ]
    Safety measured by incidence

  4. Proportion of subjects with clinical laboratory test abnormalities [ Time Frame: Approximately 28 months ]
    Safety measured by incidence

  5. Objective response rate (ORR) [ 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)

  6. Duration of Response (DOR) [ 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 ]
    Pharmacokinetics (PK) measured by summary statistics

  2. Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  3. Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  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 ]
    PK measured by summary statistics

  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 ]
    PK measured by summary statistics

  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 ]
    PK measured by summary statistics

  7. Total body clearance (CLT) of BMS-986016 administered both alone alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  8. Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with Nivolumab [ Time Frame: Approximately 28 Months ]
    PK measured by summary statistics

  9. 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 ]
    PK measured by summary statistics

  10. 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 ]
    PK measured by summary statistics

  11. 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 ]
    PK measured by summary statistics

  12. 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 ]
    PK measured by summary statistics

  13. 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 ]
    PK measured by summary statistics

  14. 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 ]
    PK measured by summary statistics

  15. Incidence of ADA to nivolumab and BMS-986016 [ Time Frame: Approximately 28 Months ]
    Immunogenicity measured by summary statistics

  16. Summary of AEs of special interest by [ Time Frame: Approximately 28 Months ]
    Immunogenicity measured by summary statistics


Eligibility Criteria
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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:

  • For dose escalation monotherapy: CLL, HL, NHL, MM
  • For dose expansion monotherapy: CLL, HL, NHL
  • For dose escalation and dose expansion in combination with BMS-936558: HL and DLBCL
  • Progressed, or been intolerant to, at least one standard treatment regimen
  • Not eligible for or declined transplantation or any standard therapy known to be life prolonging or life saving
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • At least 1 lesion with measurable disease at baseline
  • Availability of an existing tumor biopsy sample (or consent to allow pre-treatment tumor biopsy if sample not available)

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)
  • Autoimmune disease
  • Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
  • Uncontrolled or significant cardiovascular disease

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations
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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


Contacts
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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
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United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Douglas Gladstone, Site 0007    410-614-8040      
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Philippe Armand, Site 0004    617-582-8437      
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Asif Alavi, Site 0009    313-576-9376      
United States, Missouri
Washington University School Of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Nancy Bartlett, Site 0010    314-747-7402      
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: John Leonard, Site 0003    212-746-1362      
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Stephen Spurgeon, Site 0002    503-418-2086      
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sattva Neelapu, Site 0006    713-792-4887      
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay Gopal, Site 0001    206-288-2037      
Canada, British Columbia
BC Cancer Agency - Vancouver Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Kerry Savage, Site 0011    60487760002738      
Canada, Ontario
University Health Network - Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: John Kuruvilla, Site 0012    4169464501ext2445      
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
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Additional Information:
BMS Clinical Trial Information  This link exits the ClinicalTrials.gov site BMS Clinical Trial Patient Recruiting  This link exits the ClinicalTrials.gov site Investigator Inquiry Form  This link exits the ClinicalTrials.gov site FDA Safety Alerts and Recalls  This link exits the ClinicalTrials.gov site

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02061761     History of Changes
Other Study ID Numbers: CA224-022
First Posted: February 13, 2014    Key Record Dates
Last Update Posted: November 15, 2018
Last Verified: November 2018

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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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Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Hematologic Diseases
 Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents