Status:
ACTIVE_NOT_RECRUITING
Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma
Lead Sponsor:
University of Florida
Collaborating Sponsors:
Children's National Research Institute
Conditions:
Recurrent Group 3 Medulloblastoma
Recurrent Group 4 (Non-SHH/Non-WNT) Medulloblastoma
Eligibility:
All Genders
4-30 years
Phase:
PHASE1
Brief Summary
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.
Detailed Description
This is a single-site, single arm, unblinded, uncontrolled pilot study to evaluate the feasibility and safety of ACT + PD-1 blockade in children and young adults with suspected recurrence/progression ...
Eligibility Criteria
Inclusion
- 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.
- 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.
- 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)
- 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
- For females of childbearing potential, negative serum pregnancy test at enrollment
- 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.
- or For males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.
- Signed informed consent by patient and/or legally authorized representative
Exclusion
- this study:
- Prior discontinuation of PD-1 inhibitor treatment due to toxicity or disease progression.
- Corticosteroids equivalent to ≥ 4mg dexamethasone daily.
- HIV, Hepatitis B, or Hepatitis C seropositive.
- Known active infection or immunosuppressive disease.
- Autoimmune disease requiring medical management with immunosuppressant.
- Pregnancy or lactation, due to possible adverse effects on the developing fetus or infant.
- Treatment with another investigational drug or other intervention within 30 days prior to projected first dose of study treatment (Priming phase with TTRNA-DC).
- 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.
Key Trial Info
Start Date :
May 5 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2028
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT06514898
Start Date
May 5 2025
End Date
December 1 2028
Last Update
December 18 2025
Active Locations (1)
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1
University of Florida Health
Gainesville, Florida, United States, 32608