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

NCT03130959 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CA209-9082016-004441-82
• Study Type: interventional
• Target: 166
• Locations: 15 countries
• Sites: 54

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.

Conditions

Various Advanced Cancer

Outcome Measures

Primary Outcomes (6)

• Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs)

  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).

  up to 6 weeks post-dosing

• Number of Safety Lead-In Participants With Serious Adverse Events (SAEs)

  The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study.

  up to 6 weeks post-dosing

• Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation

  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.

  From first dose to 30 days post-last dose (up to approximately 6 weeks)

• Overall Survival (OS), Cohort 1 Only

  Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1.

  up to approximately 42 months

• Progression-Free Survival (PFS), Cohorts 2-4

  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.

  up to approximately 42 months

• Progression-Free Survival (PFS), Cohort 5 Only

  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.

  up to approximately 42 months

Secondary Outcomes (11)

• Progression-Free Survival (PFS), Cohort 1 Only

  From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months)

• Overall Survival at 12 Months (OS12), Cohorts 1-4

  From first dose to up to 12 months after first dose

• Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5

  From first dose to up to 6 months after first dose

• Overall Survival (OS), Cohorts 2-5

  From first dose to the date of death (up to approximately 55 months)

• Number of Treated Participants With Adverse Events (AEs)

  From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)

Study Arms (2)

Module A

EXPERIMENTAL

Biological: Nivolumab

Module B

EXPERIMENTAL

Biological: Nivolumab; Biological: Ipilimumab

Interventions

Nivolumab BIOLOGICAL

Specified dose on specified days

Also known as: Opdivo, BMS-936558

Module A; Module B

Ipilimumab BIOLOGICAL

Specified dose on specified days

Also known as: Yervoy, BMS-734016

Module B

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (54)

Local Institution - 0057

Los Angeles, California, 90027, United States

Location

Local Institution - 0016

Aurora, Colorado, 80045, United States

Location

Local Institution - 0046

Gainesville, Florida, 32611, United States

Location

Local Institution - 0011

Chicago, Illinois, 60611-2605, United States

Location

Local Institution - 0005

Baltimore, Maryland, 21287, United States

Location

Local Institution - 0043

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0044

St Louis, Missouri, 63110, United States

Location

Local Institution - 0004

New York, New York, 10021, United States

Location

Local Institution - 0017

New York, New York, 10032, United States

Location

Cincinnati Children'S Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Local Institution - 0066

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution

Charleston, South Carolina, 29425, United States

Location

Local Institution - 0012

Memphis, Tennessee, 38105, United States

Location

Local Institution - 0042

Houston, Texas, 77030, United States

Location

Local Institution - 0022

Randwick, New South Wales, 2031, Australia

Location

Local Institution - 0035

Sth Brisbane, Queensland, 4101, Australia

Location

Local Institution

Clayton, Victoria, 3168, Australia

Location

Local Institution - 0034

Parkville, Victoria, 3052, Australia

Location

Local Institution - 0033

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0052

Porto Alegre, Rio Grande do Sul, 90035-074, Brazil

Location

Local Institution - 0051

Barretos, São Paulo, 14784-400, Brazil

Location

Local Institution - 0053

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Local Institution - 0049

São Paulo, 04023-062, Brazil

Location

Local Institution - 0050

São Paulo, 08270-070, Brazil

Location

Local Institution - 0021

Toronto, Ontario, M5G 1X8, Canada

Location

Local Institution - 0001

Montreal, Quebec, H4A 3J1, Canada

Location

Local Institution - 0002

Québec, Quebec, G1V 4G2, Canada

Location

Local Institution - 0028

Angers, 49100, France

Location

Local Institution - 0029

Bordeaux, 33076, France

Location

Local Institution - 0027

Lille, 59000, France

Location

Local Institution - 0025

Lyon, 69008, France

Location

Local Institution - 0024

Marseille, 13385 cedex 05, France

Location

Local Institution - 0023

Paris, 75231 cedex 5, France

Location

Local Institution - 0064

Vandœuvre-lès-Nancy, 54500, France

Location

Local Institution - 0026

VIillejuif, 94805 CEDEX, France

Location

Local Institution - 0060

Essen, 45147, Germany

Location

Local Institution - 0061

Hamburg, 20246, Germany

Location

Local Institution - 0063

Heidelberg, 69120, Germany

Location

Local Institution - 0062

Würzburg, 97080, Germany

Location

Local Institution - 0018

Hong Kong, 852, Hong Kong

Location

Local Institution - 0059

Haifa, 3109601, Israel

Location

Local Institution - 0058

Ramat Gan, 5266202, Israel

Location

Local Institution - 0007

Rotterdam, 3015 GJ, Netherlands

Location

Local Institution - 0008

Utrecht, 3584 EA, Netherlands

Location

Local Institution - 0067

Oslo, 0027, Norway

Location

Local Institution - 0047

Warsaw, 04-730, Poland

Location

Local Institution - 0048

Moscow, 117997, Russia

Location

Local Institution - 0037

Esplugues de Llobregat, 08950, Spain

Location

Local Institution - 0038

Madrid, 28009, Spain

Location

Local Institution - 0036

Valencia, 46026, Spain

Location

Local Institution - 0065

Solna, 171 76, Sweden

Location

Local Institution - 0010

London, Greater London, WC1N 3JH, United Kingdom

Location

Local Institution - 0013

Liverpool, Merseyside, L12 2AP, United Kingdom

Location

Local Institution - 0015

Newcastle upon Tyne, Tyne and Wear, NEI 4LP, United Kingdom

Location

Related Publications (1)

• Dunkel IJ, Doz F, Foreman NK, Hargrave D, Lassaletta A, Andre N, Hansford JR, Hassall T, Eyrich M, Gururangan S, Bartels U, Gajjar A, Howell L, Warad D, Pacius M, Tam R, Wang Y, Zhu L, Cohen K. Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: Safety, efficacy, biomarker, and pharmacokinetics-CheckMate 908. Neuro Oncol. 2023 Aug 3;25(8):1530-1545. doi: 10.1093/neuonc/noad031.

  PMID: 36808285 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Interventions

Nivolumab; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 5, 2017
• First Posted: April 27, 2017
• Study Start: June 12, 2017
• Primary Completion: March 10, 2020
• Study Completion: January 17, 2022
• Last Updated: August 9, 2022
• Results First Posted: April 1, 2021

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); RU (1); IL (2); US (14); FR (8); DE (4); PL (1); BR (5); NL (2); SE (1); ES (3); CA (3); AU (5); GB (3); HK (1)