Stem Cell + Nivolumab for Pediatric Brain Tumor

(Peds CHAMP1ON Trial)

Overseen By Jennifer King, RN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Must not be taking: Investigational agents, Live vaccines

Disqualifiers: Leptomeningeal disease, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 280 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for children with certain aggressive brain tumors that have recurred or resisted standard treatments. The researchers are testing a combination of stem cells and the drug nivolumab (an immunotherapy), administered either before or after surgery, to determine if they can shrink these challenging tumors. Children diagnosed with specific high-grade brain tumors and who have experienced tumor recurrence after initial treatments might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have recovered from any recent cancer treatments and be on a stable or decreasing dose of corticosteroids for at least 7 days before joining. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nivolumab, a key component of the treatment under study, has generally been safe in past studies with children. It was used in various combinations and proved mostly safe in these trials. Some children experienced side effects, but these were usually manageable. Nivolumab has also been used for certain types of childhood cancers before, providing some confidence in its safety.

The new aspect of the treatment in this trial involves using specially prepared stem cells called ex vivo expanded CD34+ hematopoietic stem cells (exHSCs). As this is an early-stage trial, researchers are still studying the safety of using exHSCs with nivolumab. The trial aims to determine how well children can tolerate this new combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using stem cells combined with Nivolumab for pediatric brain tumors because it represents a novel approach in cancer treatment. Unlike traditional therapies that primarily target the tumor directly, this treatment leverages the body's immune system. Nivolumab is an immunotherapy drug that helps the immune system recognize and attack cancer cells more effectively, while ex vivo hematopoietic stem cells (exHSCs) may enhance this immune response. Additionally, the treatment is being tested in two different approaches: one administered before surgery to shrink the tumor and one after surgery to prevent recurrence, providing flexibility and potentially improving outcomes for young patients.

What evidence suggests that this trial's treatments could be effective for pediatric brain tumors?

Research has shown that nivolumab holds promise for treating pediatric cancers, particularly those that are difficult to treat. In previous studies, nivolumab led to lasting improvements and extended the lives of children with tough-to-treat tumors. Nivolumab aids the immune system in identifying and attacking cancer cells. In this trial, researchers are studying two approaches: one arm administers nivolumab and specially prepared stem cells (exHSCs) after surgery or biopsy, and the other arm administers them before surgery or biopsy. While the results of this combination are still under investigation, each component has shown promise in improving outcomes for challenging brain tumors. ^{2 3 5 6 7}

Who Is on the Research Team?

John Ligon, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for pediatric patients with high-grade gliomas (like astrocytoma, oligodendroglioma) that have come back or haven't responded to treatment. They must have had radiotherapy and be able to undergo surgery or a biopsy.

Inclusion Criteria

I have at least one tumor that can be measured in size.

It's been over 21 days since my last cancer treatment that affects my bone marrow.

I had my last brain and spine radiation treatment over 3 months ago.

Exclusion Criteria

I have had a stem cell transplant from a donor.

I have an autoimmune disease but it's either mild or under control with minimal treatment.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ex vivo expanded CD34+ hematopoietic stem cells (exHSCs) plus nivolumab. One cycle is 28 days, with exHSCs + Nivolumab on day 1 and Nivolumab alone on day 15, for a total of 10 cycles.

280 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Nivolumab may continue for a total of two years of therapy, at the discretion of the treating team.

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• exHSC
• Nivolumab

Trial Overview

The study tests combining expanded CD34+ hematopoietic stem cells (exHSCs) with the immunotherapy drug Nivolumab in children. It's a Phase I trial, which means it's early in testing and focuses on safety.

How Is the Trial Designed?

Group I: Neoadjuvant exHSCs + Nivolumab (starting before surgery/biopsy) (Arm 2) Experimental Treatment 3 Interventions

exHSCs + Nivolumab will be administered prior to maximal surgical resection or biopsy.

Group II: Adjuvant exHSCs + Nivolumab (starting after surgery/biopsy) (Arm 1) Experimental Treatment 3 Interventions

Immediate maximal surgical resection or biopsy, untreated tumor. exHSCs and Nivolumab will be administered after maximal surgical resection.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Florida Department of Health

Collaborator

Trials

30

Recruited

13,000+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37126021/

Efficacy of Nivolumab in Pediatric Cancers with High ...

Conclusions: Nivolumab resulted in durable responses and prolonged survival for the first time in a pediatric trial of refractory hypermutated ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10690097/

Efficacy of Nivolumab in Pediatric Cancers with High Mutation ...

Nivolumab resulted in durable responses and prolonged survival for the first time in a pediatric trial of refractory hypermutated cancers including malignant ...

3.

tp.amegroups.org

tp.amegroups.org/article/view/104755/html

Immunotherapy for the treatment of pediatric brain tumors

Long term overall survival rates for pediatric CNS tumors approach 70%. However, there remains a portion of tumor types in which survival ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02529072

Nivolumab With DC Vaccines for Recurrent Brain Tumors

This two-arm randomized trial will evaluate the safety of nivolumab in combination with DC vaccinations for the treatment of bevacizumab-naïve subjects with ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10398811/

Nivolumab with or without ipilimumab in pediatric patients with ...

In recurrent/progressive other high-grade CNS tumors (cohort 5), median OS was 5.9 (95% CI, 2.0–8.0) months with NIVO3 (n = 19) and 8.5 (95% CI, ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36808285/

Nivolumab with or without ipilimumab in pediatric patients with ...

Results: As of January 13, 2021, median OS (80% CI) was 11.7 (10.3-16.5) and 10.8 (9.1-15.8) months with NIVO and NIVO + IPI, respectively, in ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03130959

A Study to Evaluate the Safety and Efficacy of Nivolumab ...

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 ...