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A Study to Evaluate the Safety and Efficacy of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Participants With High Grade Primary Central Nervous System (CNS) Malignancies (CheckMate 908)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03130959
Recruitment Status : Completed
First Posted : April 27, 2017
Results First Posted : April 1, 2021
Last Update Posted : April 5, 2022
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE April 5, 2017
First Posted Date  ICMJE April 27, 2017
Results First Submitted Date  ICMJE March 3, 2021
Results First Posted Date  ICMJE April 1, 2021
Last Update Posted Date April 5, 2022
Actual Study Start Date  ICMJE June 12, 2017
Actual Primary Completion Date March 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2021)
  • Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: up to 6 weeks post-dosing ]
    A dose-limiting toxicity (DLT) is defined as a drug-related AE occurring in the first 6 weeks of study treatment. A participant was considered evaluable for a DLT if study treatment was delayed > 2 weeks or was discontinued due to a related Adverse Event (AE), or if planned study treatment (3 doses of nivolumab in Module A, 2 doses of nivolumab plus ipilimumab in Module B) was administered and safety evaluation after 6 weeks on study is available to the study steering committee (SSC).
  • Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) [ Time Frame: up to 6 weeks post-dosing ]
    The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study.
  • Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation [ Time Frame: up to 6 weeks post-dosing ]
    The number of Safety Lead-In Participants who experienced an Adverse Event (AE) during the course of the study that lead to discontinuation of study therapy.
  • Overall Survival (OS), Cohort 1 Only [ Time Frame: up to approximately 42 months ]
    Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1.
  • Progression-Free Survival (PFS), Cohorts 2-4 [ Time Frame: up to approximately 42 months ]
    Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
  • Progression-Free Survival (PFS), Cohort 5 Only [ Time Frame: up to approximately 42 months ]
    Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • Incidence of dose limiting toxicity (DLT) [ Time Frame: Approximately 6 weeks ]
    Safety and tolerability
  • Incidence of serious adverse events (SAEs) [ Time Frame: Approximately 6 weeks ]
    Safety and tolerability
  • Incidence of adverse events (AEs) [ Time Frame: Approximately 6 weeks ]
    Safety and tolerability
  • Overall Survival (OS) [ Time Frame: Approximately 3 years ]
    Diffuse Intrinsic Pontine Glioma (DIPG).
  • Progression Free Survival (PFS) [ Time Frame: Approximately 2 years ]
    All other tumor types.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
  • Progression-Free Survival (PFS), Cohort 1 Only [ Time Frame: up to approximately 42 months ]
    Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
  • Overall Survival at 12 Months (OS12), Cohorts 1-4 [ Time Frame: up to 12 months ]
    Overall survival at 12 months (OS12) is defined as the percentage of participants who are alive at 12 months, measured as the survival rate at 12 months from Kaplan-Meier product limit cumulative probability.
  • Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 [ Time Frame: up to 6 months ]
    Progression-free survival at 6 months (PFS6) is defined as the percentage of participants who are progression free and alive at 6 months following first dose date, measured as the survival rate at 6 months from Kaplan-Meier product limit cumulative probability of progression free.
  • Overall Survival (OS), Cohorts 2-5 [ Time Frame: up to approximately 42 months ]
    Overall survival (OS) is defined as the time between date of first dose and the date of death for Cohorts 2-5.
  • Number of Treated Participants With Adverse Events (AEs) [ Time Frame: from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced an Adverse Event (AE) during the course of the study.
  • Number of Treated Participants With Serious Adverse Events (SAEs) [ Time Frame: from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced a Serious Adverse Event (SAE) during the course of the study. Note: The reporting timeframe of the SAEs for this Outcome Measure (first dose to 30 days post last dose) differs than that of the reporting timeframe of the SAEs reported under the AE section of the results form (first dose to 100 days post last dose) and thus, the data in each table of SAEs reflects the specific timeframe applied.
  • Number of Treated Participants With Drug-Related Adverse Events [ Time Frame: from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced a Drug-Related Adverse Event during the course of the study.
  • Number of Treated Participants With Adverse Events Leading to Discontinuation [ Time Frame: from first dose to 30 days post-last dose, assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced an Adverse Event leading to discontinuation during the course of the study.
  • Number of Treated Participant Deaths [ Time Frame: from first dose assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who died during the course of the study.
  • Number of Treated Participant With Laboratory Abnormalities - Liver [ Time Frame: from first dose assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
  • Number of Treated Participant With Laboratory Abnormalities - Thyroid [ Time Frame: from first dose assessed up to 13Jan2021 (up to approximately 42 months) ]
    The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study. Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • Incidence of AEs [ Time Frame: Approximately 3 years ]
    Safety
  • Incidence of SAEs [ Time Frame: Approximately 3 years ]
    Safety
  • Incidence of laboratory abnormalities [ Time Frame: Approximately 3 years ]
    Safety
  • Progression Free Survival (PFS) [ Time Frame: 18 months to 24 months ]
    Diffuse Intrinsic Pontine Glioma (DIPG)
  • Overall Survival [ Time Frame: Approximately 12 months ]
    Diffuse Intrinsic Pontine Glioma (DIPG). Overall Survival at 12 month point (OS(12)).
  • Progression Free Survival [ Time Frame: Approximately 6 months ]
    High Grade Glioma (HGG), Medulloblastoma, Ependymoma, and other high-grade CNS tumors. At 6 months (PFS(6)).
  • Overall Survival (OS) [ Time Frame: Approximately 3 years ]
    High Grade Glioma (HGG), Medulloblastoma, Ependymoma, and other high-grade CNS tumors.
  • Overall Survival [ Time Frame: Approximately 12 months ]
    High Grade Glioma (HGG), Medulloblastoma, Ependymoma. At 12 month point (OS(12)).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Efficacy of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Participants With High Grade Primary Central Nervous System (CNS) Malignancies
Official Title  ICMJE Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies
Brief Summary The purpose of this study is to determine the safety and effectiveness of nivolumab alone and in combination with ipilimumab in pediatric patients with high grade primary central nervous system (CNS) malignancies.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Various Advanced Cancer
Intervention  ICMJE
  • Biological: Nivolumab
    Specified dose on specified days
    Other Name: Opdivo, BMS-936558
  • Biological: Ipilimumab
    Specified dose on specified days
    Other Name: Yervoy, BMS-734016
Study Arms  ICMJE
  • Experimental: Module A
    Intervention: Biological: Nivolumab
  • Experimental: Module B
    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 26, 2021)
166
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2017)
170
Actual Study Completion Date  ICMJE January 17, 2022
Actual Primary Completion Date March 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must have received standard of care therapy, and there must be no potentially-curative treatment available, in one of the following cohorts:
  • A newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) that has been treated with radiation therapy (RT) but no chemotherapy
  • A histologically confirmed recurrent or progressive non-brainstem High Grade Glioma (HGG) previously treated with surgical resection and RT
  • A histologically confirmed medulloblastoma that has relapsed or is resistant to at least one line of prior therapy including surgery, RT, and chemotherapy
  • A histologically confirmed ependymoma that has relapsed or is resistant to at least one line of prior therapy including surgical resection and RT
  • A histologically-confirmed high grade CNS malignancy "other than above" which is recurrent or progressive after at least one line of prior therapy
  • Lansky play score (LPS) for ≤ 16 years of age or Karnofsky performance scale (KPS) for > 16 years of age assessed within two weeks of enrollment must be >= 60
  • A tumor sample must be available for submission to central laboratory (not required for DIPG)

Exclusion Criteria:

  • An active, known, or suspected autoimmune disease
  • A concurrent condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Other protocol defined inclusion/exclusion criteria apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Canada,   France,   Germany,   Hong Kong,   Israel,   Netherlands,   Norway,   Poland,   Russian Federation,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03130959
Other Study ID Numbers  ICMJE CA209-908
2016-004441-82 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date March 2022

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