NCT06514898 · University of Florida
Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma
(MATCHPOINT)
What this study is about
This is a pilot study in a small number of children and young adults with suspected recurrent/progressive medulloblastoma (MB) looking at the feasibility and safety of adoptive cell therapy plus PD-1 blockade.
View original scientific description
This is a pilot study in a small number of children and young adults with suspected recurrent/progressive medulloblastoma (MB) looking at the feasibility and safety of adoptive cell therapy plus PD-1 blockade.
Interventions
BIOLOGICAL
TTRNA-DC vaccines with GM-CSF
After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. up to 9 intradermal DC vaccines (three -bi-weekly (q2 weeks) for priming, monthly for additional 2-3 cycles during T cell expansion, and three bi-weekly during T cell engraftment)
BIOLOGICAL
TTRNA-xALT
All participants will receive a single infusion of T-cells.
DRUG
Td vaccine
A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #5, #7 and #9.
BIOLOGICAL
autologous HSCs
All participants will receive a single intravenous infusion of autologous HSCs.
DRUG
Pembrolizumab
Participants will receive PD-1 blockade IV starting with ACT continuing for up to 2 years as long as tolerable and without disease progression.
Primary outcome measures
Number of participants with immunotherapy-related dose-limiting toxicities after treatment with TTRNA-DCs, TTRNA-xALT and HSCs plus PD1 blockade
Time frame: enrollment to completion of DLT window; up to 12 months
Number of subjects with immunotherapy-related dose-limiting toxicities including 1) Grade III or greater non-neurologic toxicity; 2) Grade III neurologic toxicity that does not improve to Grade II or better within 5 days; or 3) Grade IV neurologic toxicity. For the purposes of evaluating the safety of ACT combined with PD-1 blockade, dose limiting toxicities will be assessed during the period beginning with administration of ex vivo expanded tumor-reactive (TTRNA- xALT) through 2 weeks post TTRNA -DC vaccine #9. Safety will be defined as \< 1 DLT out of six enrolled and treated subjects.
Number of enrolled participants who receive qualified immunotherapy products out of the total number of participants enrolled.
Time frame: enrollment up to 12 months
Feasibility will be defined as capacity to enroll, manufacture, and administer qualified immunotherapy products (TTRNA-DCs, TTRNA-xALT and HSCs) to at least 66.7% of enrolled subjects.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Children and young adults ages 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.
- Patients must currently be prescribed and approved to receive pembrolizumab therapy (patients who have progressed on anti-PD-1 targeting therapy but are otherwise eligible may be enrolled to receive combination with immunotherapy. Patients who have been previously treated with anti-PD-1 targeting therapy alone or in combination with other agents and discontinued for reasons other than toxicity may be enrolled).
- Must be a candidate for surgery/biopsy Or tumor tissue obtained clinically, has been previously stored in a qualified 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 criteria
- this study:
- Prior discontinuation of PD-1 inhibitor treatment due to toxicity.
- Corticosteroids equivalent to ≥ 4mg dexamethasone daily.
- Known HIV, Hepatitis B, or Hepatitis C seropositive.
- Known active infection or immunosuppressive disease.
- Known 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).
- Known 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.
Where
- Gainesville, Florida
Collaborators
Children's National Research Institute
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 10, 2026 · Source of record for eligibility and locations