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

Inclusion Criteria17

• 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