ACTIVE_NOT_RECRUITING

Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma

Conditions

Recurrent Group 3 Medulloblastoma Recurrent Group 4 (Non-SHH/Non-WNT) Medulloblastoma

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 pilot study in a small number of children and young adults with relapsed/progressive medulloblastoma (MB) looking at the feasibility and safety of adoptive cell therapy plus PD-1 blockade.

Official Title

MATCHPOINT - Medulloblastoma Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade

Quick Facts

Study Start:2025-05-05

Study Completion:2028-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06514898

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 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Children and young adults age 4-30 years with suspected recurrence/progression of Group 3 or 4 (non-SHH/non-WNT) MB since completion of definitive focal +/- craniospinal irradiation who are a candidate for surgical resection or biopsy. Of the 6 evaluable subjects, a minimum of 3 slots must be reserved for patients with confirmed Group 4 MB. Patients who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome or NF1 mutation) are eligible for enrollment at first disease recurrence/progression. 2. Must be a candidate for surgery/biopsy Or tumor tissue obtained clinically, has been previously stored in a biorepository suitable for tumor RNA extraction and amplification and sample is made available to the PI. 3. Karnofsky or Lansky Performance Status (KPS) ≥ 60% (KPS for \> 16 years of age) or Lansky performance Score (LPS) of ≥ 60 (LPS for \< 16 years of age) 4. Adequate bone marrow and organ function as defined below: * ANC ≥ 1,000/mcL (unsupported) * Platelets ≥ 100,000/mcL (unsupported for at least 3 days) * Hemoglobin ≥ 9 g/dL (may be supported) * Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine \> 1.5 x IULN * Serum total bilirubin ≤ 1.5 x IULN for age OR Direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN for age * AST (SGOT) and ALT (SGPT) ≤ 3 x IULN for age * Cardiac shortening fraction ≥27% or LVEF ≥50% by echocardiogram * Adequate pulmonary function defined as baseline pulse oximetry of ≥92% on room air 5. For females of childbearing potential, negative serum pregnancy test at enrollment 6. For women of childbearing potential (WOCBP) must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug. 7. Signed informed consent by patient and/or legally authorized representative	1. Prior discontinuation of PD-1 inhibitor treatment due to toxicity or disease progression. 2. Corticosteroids equivalent to ≥ 4mg dexamethasone daily. 3. HIV, Hepatitis B, or Hepatitis C seropositive. 4. Known active infection or immunosuppressive disease. 5. Autoimmune disease requiring medical management with immunosuppressant. 6. Pregnancy or lactation, due to possible adverse effects on the developing fetus or infant. 7. Treatment with another investigational drug or other intervention within 30 days prior to projected first dose of study treatment (Priming phase with TTRNA-DC). 8. Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization. * Transmural myocardial infarction within the last 6 months. * Acute bacterial or fungal infection requiring intravenous antibiotics at time of enrollment. * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy. * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. * Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. * Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.

Inclusion Criteria

Exclusion Criteria

1. Children and young adults age 4-30 years with suspected recurrence/progression of Group 3 or 4 (non-SHH/non-WNT) MB since completion of definitive focal +/- craniospinal irradiation who are a candidate for surgical resection or biopsy. Of the 6 evaluable subjects, a minimum of 3 slots must be reserved for patients with confirmed Group 4 MB. Patients who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome or NF1 mutation) are eligible for enrollment at first disease recurrence/progression.
2. Must be a candidate for surgery/biopsy Or tumor tissue obtained clinically, has been previously stored in a biorepository suitable for tumor RNA extraction and amplification and sample is made available to the PI.
3. Karnofsky or Lansky Performance Status (KPS) ≥ 60% (KPS for \> 16 years of age) or Lansky performance Score (LPS) of ≥ 60 (LPS for \< 16 years of age)
4. Adequate bone marrow and organ function as defined below:
* ANC ≥ 1,000/mcL (unsupported)
* Platelets ≥ 100,000/mcL (unsupported for at least 3 days)
* Hemoglobin ≥ 9 g/dL (may be supported)
* Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine \> 1.5 x IULN
* Serum total bilirubin ≤ 1.5 x IULN for age OR Direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN for age
* AST (SGOT) and ALT (SGPT) ≤ 3 x IULN for age
* Cardiac shortening fraction ≥27% or LVEF ≥50% by echocardiogram
* Adequate pulmonary function defined as baseline pulse oximetry of ≥92% on room air
5. For females of childbearing potential, negative serum pregnancy test at enrollment
6. For women of childbearing potential (WOCBP) must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
7. Signed informed consent by patient and/or legally authorized representative

1. Prior discontinuation of PD-1 inhibitor treatment due to toxicity or disease progression.
2. Corticosteroids equivalent to ≥ 4mg dexamethasone daily.
3. HIV, Hepatitis B, or Hepatitis C seropositive.
4. Known active infection or immunosuppressive disease.
5. Autoimmune disease requiring medical management with immunosuppressant.
6. Pregnancy or lactation, due to possible adverse effects on the developing fetus or infant.
7. Treatment with another investigational drug or other intervention within 30 days prior to projected first dose of study treatment (Priming phase with TTRNA-DC).
8. Severe, active co-morbidity, defined as follows:
* Unstable angina and/or congestive heart failure requiring hospitalization.
* Transmural myocardial infarction within the last 6 months.
* Acute bacterial or fungal infection requiring intravenous antibiotics at time of enrollment.
* Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy.
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
* Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
* Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.

Contacts and Locations

Principal Investigator

Duane Mitchell, MD, PhD

STUDY_CHAIR

University of Florida

John Ligon, MD

PRINCIPAL_INVESTIGATOR

University of Florida

Study Locations (Sites)

University of Florida Health

Gainesville, Florida, 32608

United States

Collaborators and Investigators

Sponsor: University of Florida

Duane Mitchell, MD, PhD, STUDY_CHAIR, 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 Date2025-05-05

Study Completion Date2028-12-01

Study Record Updates

Study Start Date2025-05-05

Study Completion Date2028-12-01

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Group 3 Medulloblastoma
Recurrent Group 4 (Non-SHH/Non-WNT) Medulloblastoma