RECRUITING

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

Conditions

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

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2025-08

Study Completion:2032-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07031765

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:4 Years to 26 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * 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 * Patients must have adequate organ and marrow function as defined below: * Absolute neutrophil count \>1000 cells/μL * Platelets \>75,000 cells/μL(unsupported, defined as no platelet transfusion within 7 days) * Hemoglobin ≥8g/dl (may receive transfusions) * Total bilirubin ≤1.5 times institutional upper limit of normal (ULN) * ALT(SGPT) \<3 x institutional upper limit of normal * Albumin ≥2 g/dl * Serum creatinine based on age/gender as noted in Table 1 Patients that do not meet the criteria below but have a 24hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 ml/min/1.73 m2 are eligible. * INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * Pulmonary function - Pulse oximetry \> 93% on room air and no evidence of dyspnea at rest. * Patient must be a candidate for surgical resection or biopsy at the time of enrollment. The goal of surgical resection is both cytoreduction and tumor debulking, or biopsy for diagnosis confirmation as part of standard of care. * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. A baseline detailed neurological exam should clearly document the neurological status of the patient at the time of enrollment on the study. * Patients must be on a stable or decreasing dose of corticosteroids for 7 days prior to enrollment. A maximum dexamethasone dose of 0.1 mg/kg/day is allowed (4 mg maximum), but preferably have been discontinued (inhaled or topical use of steroids is allowed). * The effects of nivolumab on the developing human fetus are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months after completion of nivolumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 5 months after completion of nivolumab administration.	* 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.

Inclusion Criteria

Exclusion Criteria

* 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
* 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
* Patients must have adequate organ and marrow function as defined below:
* Absolute neutrophil count \>1000 cells/μL
* Platelets \>75,000 cells/μL(unsupported, defined as no platelet transfusion within 7 days)
* Hemoglobin ≥8g/dl (may receive transfusions)
* Total bilirubin ≤1.5 times institutional upper limit of normal (ULN)
* ALT(SGPT) \<3 x institutional upper limit of normal
* Albumin ≥2 g/dl
* Serum creatinine based on age/gender as noted in Table 1 Patients that do not meet the criteria below but have a 24hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 ml/min/1.73 m2 are eligible.
* INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
* aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
* Pulmonary function - Pulse oximetry \> 93% on room air and no evidence of dyspnea at rest.
* Patient must be a candidate for surgical resection or biopsy at the time of enrollment. The goal of surgical resection is both cytoreduction and tumor debulking, or biopsy for diagnosis confirmation as part of standard of care.
* Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. A baseline detailed neurological exam should clearly document the neurological status of the patient at the time of enrollment on the study.
* Patients must be on a stable or decreasing dose of corticosteroids for 7 days prior to enrollment. A maximum dexamethasone dose of 0.1 mg/kg/day is allowed (4 mg maximum), but preferably have been discontinued (inhaled or topical use of steroids is allowed).
* The effects of nivolumab on the developing human fetus are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months after completion of nivolumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 5 months after completion of nivolumab administration.

* 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.

Contacts and Locations

Study Contact

Marcia Hodik, BSHS

CONTACT

352-273-6971

marcia.hodik@neurosurgery.ufl.edu

Principal Investigator

John Ligon, MD

PRINCIPAL_INVESTIGATOR

University of Florida

Study Locations (Sites)

UF Health Shands Children's Hospital/Shands Hospital

Gainesville, Florida, 32608

United States

Collaborators and Investigators

Sponsor: University of Florida

John Ligon, MD, PRINCIPAL_INVESTIGATOR, University of Florida

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-08

Study Completion Date2032-12

Study Record Updates

Study Start Date2025-08

Study Completion Date2032-12

Terms related to this study

Additional Relevant MeSH Terms

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