Combining T Cell Therapy and Vaccines with Immune Blockade for Medulloblastoma

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

This study is testing a new treatment that combines special immune cell therapy and vaccines to see if it can help children and young adults with recurring medulloblastoma feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 4 Years to 30 Years
• Sex: All
• Sponsor: University of Florida (Academic / other)
• Drugs / interventions: radiation, chemotherapy, immunotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Gainesville, Florida)
• Trial ID: NCT06514898 on ClinicalTrials.gov

What this trial studies

This pilot study evaluates the feasibility and safety of combining adoptive T cell therapy with PD-1 blockade in children and young adults with recurrent Group 3 or 4 medulloblastoma. Participants will undergo tumor resection or biopsy to confirm disease progression, followed by the collection of tumor tissue for vaccine development. After surgery, patients will receive standard salvage chemotherapy and then be treated with tumor RNA-pulsed dendritic cell vaccines and hematopoietic stem cells. The study aims to assess the potential of this combined approach to improve outcomes in this patient population.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 4-30 years with suspected recurrence of Group 3 or 4 medulloblastoma who are eligible for surgical intervention.

Not a fit: Patients with other types of medulloblastoma or those who are not candidates for surgery or biopsy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel treatment option that enhances the immune response against medulloblastoma.

How similar studies have performed: While this approach is innovative, similar studies combining immunotherapy with other treatments have shown promise, indicating potential for success.

Eligibility criteria

Inclusion 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.

   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.
7. Signed informed consent by patient and/or legally authorized representative

Exclusion Criteria:

this study:

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.

Where this trial is running

Gainesville, Florida

• University of Florida Health — Gainesville, Florida, United States (Recruiting)

Study contacts

• Principal investigator: John Ligon, MD — University of Florida
• Study coordinator: Marcia Hodik, RN

Conditions Recurrent Group 3 Medulloblastoma; Recurrent Group 4 Medulloblastoma