Peds CHAMP1ON - Hematopoietic Stem Cell And Monoclonal Antibody PD-1 Blockade for RecurreNt Pediatric High-Grade Glioma

NCT07031765 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 20252524OCR47280
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I study of ex vivo expanded CD34+ hematopoietic stem cells (exHSCs) plus nivolumab in pediatric patients with histologically confirmed diagnosis of a non-brainstem high-grade glioma (NB-HGG, WHO Grade III or IV astrocytoma, oligodendrogliomas, oligoastrocytomas, ependymomas) that is recurrent, progressive or refractory following radiotherapy with or without chemotherapy. Patients must be candidates for standard of care surgical resection or biopsy.

Conditions

Recurrent High-grade Glioma; Oligodendroglioma; Oligoastrocytoma; Grade III Astrocytoma; Ependymoma; Grade IV Astrocytoma

Outcome Measures

Primary Outcomes (2)

• Rate of DLTs in treated participants

  Rate of DLTs in participants treated with exHSCs + αPD-1. Cycle 1 Day 1 is the first day exHSCs + Nivo is given.

  At the end of Cycle 1 (each cycle is 28 days)

• Rate of ability to manufacture a product that meets release specifications and deliver the first study treatment

  Feasibility of delivering exHSCs + αPD-1. Cycle 1 Day 1 is the first day exHSCs + Nivo is given.

  At the end of Cycle 1 (each cycle is 28 days)

Study Arms (2)

Adjuvant exHSCs + Nivolumab (starting after surgery/biopsy) (Arm 1)

EXPERIMENTAL

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

Biological: exHSC; Drug: Nivolumab; Procedure: Resection or biopsy

Neoadjuvant exHSCs + Nivolumab (starting before surgery/biopsy) (Arm 2)

EXPERIMENTAL

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

Biological: exHSC; Drug: Nivolumab; Procedure: Resection or biopsy

Interventions

exHSC BIOLOGICAL

Ex vivo expanded CD34+ hematopoietic stem cells (exHSCs) at a targeted dose of 2.5 x 106 cells/kg (or maximal achievable dose, with a minimum deliverable dose of 1/10 target dose; max dose 1.0 x 108 total cells for patients ≥40kg).

Adjuvant exHSCs + Nivolumab (starting after surgery/biopsy) (Arm 1); Neoadjuvant exHSCs + Nivolumab (starting before surgery/biopsy) (Arm 2)

Nivolumab DRUG

Nivolumab 3mg/kg once every 2 weeks, max dose 240mg. Nivolumab will be administered on day 1 and day 15 of each cycle for a total of 10 cycles. Nivolumab may continue for a total two years of therapy, at the discretion of the treating team.

Adjuvant exHSCs + Nivolumab (starting after surgery/biopsy) (Arm 1); Neoadjuvant exHSCs + Nivolumab (starting before surgery/biopsy) (Arm 2)

Resection or biopsy PROCEDURE

Patients must be candidates for standard of care surgical resection or biopsy.

Adjuvant exHSCs + Nivolumab (starting after surgery/biopsy) (Arm 1); Neoadjuvant exHSCs + Nivolumab (starting before surgery/biopsy) (Arm 2)

Eligibility Criteria

• Age: 4 Years - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have a histologically confirmed diagnosis of a non-brainstem high-grade glioma (NB-HGG, WHO Grade III or IV astrocytoma, oligodendrogliomas, oligoastrocytomas, ependymomas) that is recurrent, progressive or refractory following radiotherapy with or without chemotherapy. Patients must be candidates for standard of care surgical resection or biopsy.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in two dimensions.
• Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 2 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy or any other treatment modality prior to entering this study.
• Patients must have received their last dose of known myelosuppressive anticancer therapy greater than 21 days prior to enrollment.
• Patients must have received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment.
• For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration must be discussed with and approved by the study chair.
• Monoclonal antibody treatment and/or agents with prolonged half-lives: At least three half-lives must have elapsed prior to enrollment.
• Patients must have had their last fraction of:
• Craniospinal irradiation ≥ 3 months prior to enrollment.
• Other substantial bone marrow irradiation ≥6 weeks prior to enrollment
• Local palliative XRT ≥2 weeks
• ≥ 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment
• \*Patients with any history of allogeneic transplant are not eligible
• Patient must be ≥ 4 but ≤ 26 years of age at the time of enrollment.
• Karnofsky ≥ 60% for \> 16 years of age; Lansky ≥ 60% for children ≤ 16 years of age

You may not qualify if:

• Patients with evidence of leptomeningeal, primary spinal cord, or multicentric disease.
• Patients who have not recovered to ≤ Grade 1 or baseline from adverse events due to prior anti-cancer therapy.
• Patients who are receiving any other investigational agents.
• Female subjects of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
• Prior treatment with an anti-PD-1, anti PD-L1 and anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Patients who have had prior allogenic hematopoietic stem cell transplant.
• Participants with an active, known, or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Patients with uncontrolled intercurrent illness or any other significant condition(s) (serious infections or significant psychiatric, cardiac, pulmonary, hepatic, or other organ dysfunction that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity, or would interfere with the study procedures or results.
• Patients who have had live vaccines within 30 days prior to the first dose of trial treatment.

Sponsors & Collaborators

• University of Florida: lead
• Florida Department of Health: collaborator

Study Sites (1)

UF Health Shands Children's Hospital/Shands Hospital

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Glioma; Astrocytoma; Oligodendroglioma; Ependymoma; Glioblastoma

Interventions

Nivolumab; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• John Ligon, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: June 22, 2025
• Study Start: July 25, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2032
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)