Adoptive Cell Therapy (TTRNA-xALT), Dendritic Cell Vaccine (TTRNA-DC), and Hematopoietic Stem Cells in Combination with Pembrolizumab for the Treatment of Relapsed or Progressive Group 3 or 4 Non-SHH/Non-WNT Medulloblastoma, MATCHPOINT Trial

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 neurofibromatosis type 1 [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 site in a manner suitable for tumor RNA extraction and amplification and sample is made available to the principal investigator (PI)
• Karnofsky or Lansky performance status (Karnofsky performance status [KPS]) ≥ 60% (KPS for > 16 years of age) or Lansky performance score (LPS) of ≥ 60 (LPS for < 16 years of age)
• Absolute neutrophil count (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 institutional upper limit of normal (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
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x IULN for age
• Cardiac shortening fraction ≥ 27% or left ventricular ejection fraction (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

• 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), other than pembrolizumab
• 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 Centers for Disease Control and Prevention (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