Study Stopped
Inadequate accrual rate
Testing the Combination of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) in Children, Adolescent, and Young Adult Patients With Relapsed/Refractory Cancers That Have an Increased Number of Genetic Changes, The 3CI Study
3CI Study: Childhood Cancer Combination Immunotherapy. Phase Ib and Expansion Study of Nivolumab Combination Immunotherapy in Children, Adolescent and Young Adult (CAYA) Patients With Relapsed/Refractory Hypermutant Cancers
4 other identifiers
interventional
N/A
2 countries
9
Brief Summary
This phase Ib trial investigates the side effects of the combination of nivolumab and ipilimumab, and to see how well they work in treating patients with cancers that have come back (relapsed) or does not respond to treatment (refractory) and have an increased number of genetic changes. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Tumor mutational burden (TMB) is the total amount of genetic changes or "mutations" found in tumor cells. Some studies in adults with cancer have shown that patients with a higher TMB (an increased number of genetic changes) are more likely to respond to immunotherapy drugs. There is also evidence that nivolumab and ipilimumab can shrink or stabilize cancer in adult patients with cancer. This study is being done to help doctors learn if the combination of nivolumab and ipilimumab can help children, adolescents, and young adults patients live longer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Jan 2021
9 active sites
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 4, 2020
CompletedFirst Posted
Study publicly available on registry
August 5, 2020
CompletedStudy Start
First participant enrolled
January 28, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 21, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 21, 2022
CompletedSeptember 10, 2025
September 1, 2025
1.4 years
August 4, 2020
September 9, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events
Graded by the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
Up to 30 days after last dose of study drug
Secondary Outcomes (4)
Objective overall response rate (ORR)
Up to 1 year
Clinical benefit rate (CBR)
Up to 1 year
Progression-free survival
From study entry until documented disease progression or death, assessed up to 1 year
Overall survival
From study entry or initial diagnosis until death from any cause, assessed up to 1 year
Study Arms (2)
Dose level -1 (nivolumab)
EXPERIMENTALPART I: Patients undergo collection of tissue samples for TMB level. Patients with elevated TMB may be eligible for Part II. PART II: Patients receive nivolumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
Dose level 1 (nivolumab, ipilimumab)
EXPERIMENTALPART I: Patients undergo collection of tissue samples for TMB level. Patients with elevated TMB may be eligible for Part II. PART II: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 23 cycles in the absence of disease progression or unacceptable toxicity.
Interventions
Undergo collection of tissue samples
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- PART 1: Patients must have histologically or cytologically confirmed malignancy at the time of initial diagnosis, relapse, or recurrence. Patients must have recurrent or refractory cancer for which standard curative or palliative measures do not exist or are no longer effective
- Patients with multiple concurrent and/or sequential neoplasms are eligible
- Patients with central nervous system (CNS) tumors are eligible, except those with diffuse intrinsic pontine glioma
- Patients with lymphoma are eligible; patients with leukemia are excluded
- Chemotherapy-naive patients are eligible in cases where first-line therapy does not include chemotherapy (e.g., surgery only for ependymoma management)
- PART 1: Patients must have evidence of one or more of the following criteria in current or previous tumor:
- Microsatellite instability (MSI-H)
- Mutation causing functional loss of mismatch repair gene expression (MLH1, MSH2, MSH6, PMS2, EPCAM, MSH3)
- Hypermutation in any tumor (including primary malignancy for patients with relapse or previous cancer diagnoses)
- Functional mutation of POLE or POLD1 genes
- A syndrome linked to hypermutant cancer predisposition such as congenital mismatch repair deficiency (CMMRD), Lynch syndrome, or xeroderma pigmentosum (XP) is also permitted
- Other factors or sequencing evidence not listed above but which may be predictive of hypermutant cancer may be permitted after discussion with the protocol principal investigator
- PART 1: A tumor tissue specimen must be provided for molecular profiling, including TMB analysis. The specimen may be archival or prospective, from a medically necessary surgery, biopsy, or excision. Tissue will not be obtained solely for this trial. A specimen from the time of most recent relapse/progression is preferred, but not mandatory
- Tissue is preferred. However, if necessary, previously extracted DNA may be used with the approval of the protocol principal investigator if extracted in a clinically certified laboratory and prepared in an Foundation Medicine Inc. (FMI), TMB assay-compatible manner
- PART 1: All patients and/or their parents or legally authorized representatives must have the ability to understand and the willingness to sign a written informed consent. Assent, where appropriate, will be obtained according to local policy. Patients with impaired decision-making capacity will not be excluded
- +48 more criteria
You may not qualify if:
- PART 1: Patients with history of autoimmune disease
- PART 1: Patients with history of interstitial lung disease or pneumonitis are not eligible
- PART 1: Patients who have received solid organ transplant or allogenic stem cell transplant are not eligible
- PART 1: Patients who have been previously treated with a combination of anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors are not eligible
- PART 2: Patients requiring systemic corticosteroids or other forms of immunosuppressive therapy within 7 days prior to treatment initiation are not eligible
- Following treatment initiation, systemic corticosteroids or other forms of immunosuppressive therapy are permitted if administered for the treatment of toxicity, tumor flare, or pseudo-progression and can be tapered. In most cases study treatment must be held until the dose is tapered to 10 mg/day prednisone or equivalent. The protocol principal investigator must be consulted prior to resuming treatment
- Physiologic corticosteroids up to 5 mg/day prednisone or equivalent are permitted
- Topical, ocular, intra-articular, intra-nasal, inhaled corticosteroids are permitted
- Patients with CNS tumors receiving steroids for intracranial mass effect must be able to discontinue these at least 7 days prior to treatment initiation
- PART 2: Patients who are receiving other anticancer agent(s) are not eligible
- PART 2: Patients who are receiving or have received any other investigational agent(s) within 14 days prior to treatment initiation are not eligible
- PART 2: Patients with CNS tumors with any of the following characteristics on imaging are not eligible:
- Tumor with any evidence of uncal herniation or mass effect leading to severe midline shift
- Tumor \> 6 cm in single maximal dimension
- Tumor that in the opinion of the investigator shows significant mass effect
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792, United States
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel A Morgenstern
Cancer Immunotherapy Trials Network
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 4, 2020
First Posted
August 5, 2020
Study Start
January 28, 2021
Primary Completion
June 21, 2022
Study Completion
June 21, 2022
Last Updated
September 10, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.