Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor
Condition: Medulloblastoma; Neuroectodermal Tumor
MeSH terms: Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive
Intervention: TTRNA-xALT; TTRNA-DCs
Intervention description: TTRNA-xALT 3 x 10^7/kg by intravenous injection once.; TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Maximum age: 30 Years
Healthy volunteers: No
Keywords: Medulloblastoma; Primitive Neuroectodermal Tumor

Summary:

      Immunotherapy is a specific approach to treating cancer that has shown promise in adult
      patients for the treatment of melanoma, malignant brain tumors, and other cancers. The study
      investigators will use the experience they have gained from these studies to try to improve
      the outcome for children affected by a recurrent brain tumor.

      Approximately 35 patients with first recurrence of medulloblastoma (reMB)/supratentorial
      primitive neuroectodermal tumors (PNETs) will be treated with tumor-specific immune cells and
      dendritic cell vaccines to see what impact they have on the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

        Screening:

          -  Age ≤ 30 years of age.

          -  Suspected first recurrence/progression of MB/PNET since completion of definitive focal
             +/- craniospinal irradiation. Disease progression prior to receiving definitive focal
             +/- craniospinal irradiation will not disqualify patients from enrollment if they have
             subsequently failed definitive radiotherapy and are at first recurrence/progression at
             time of enrollment. 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.

        Re-MATCH Protocol:

          -  Patients must have histologically confirmed recurrent MB/PNET that is a first
             relapse/progression after completion of definitive radiotherapy +/- craniospinal
             irradiation. Patients with a first relapse/progression who are unable to receive
             radiation therapy due to genetic disorders that put them at significant risk for
             radiation-induced secondary malignancies (ie. Gorlin's syndrome or NF1 mutation) are
             eligible for enrollment.

          -  Patients with neurological deficits should have deficits that are stable for a minimum
             of 1 week prior to registration.

          -  Karnofsky Performance Status of ≥ 50% or Lansky Performance Score of ≥ 50.

          -  Absolute Neutrophil Count (ANC) ≥ 1000/µl (unsupported).

          -  Platelets ≥ 100,000/µl (unsupported).

          -  Hemoglobin > 8 g/dL (may be supported).

          -  Serum creatinine ≤ upper limit of institutional normal

          -  Bilirubin ≤ 1.5 times upper limit of normal for age.

          -  Serum Glutamic Oxaloacetic Transaminase (ALT) ≤ 3 times institutional upper limit of
             normal for age.

          -  Serum Glutamic Oxaloacetic Transaminase (AST) ≤ 3 times institutional upper limit of
             normal for age.

          -  Patients of childbearing or child-fathering potential must be willing to use a
             medically acceptable form of birth control, which includes abstinence, while being
             treated on this study.

          -  Patient or patient guardian consent to peripheral blood stem cell (PBSC) and/or bone
             marrow harvest following registration if PBSC or bone marrow (CD34 count of at least
             2x10^6/kg) has not been previously stored and available for use.

          -  Signed informed consent according to institutional guidelines must be obtained prior
             to registration.

        Exclusion Criteria:

          -  Pregnant or need to breast feed during the study period.

          -  Active infection requiring treatment or an unexplained febrile (> 101.5F) illness.

          -  Known immunosuppressive disease, human immunodeficiency virus infection, or carriers
             of Hepatitis B or Hepatitis C virus.

          -  Patients with active renal, cardiac (congestive cardiac failure, myocardial
             infarction, myocarditis), or pulmonary disease.

          -  Patients receiving concomitant immunosuppressive agents for medical condition.

          -  Patients who need definitive radiotherapy for treatment of recurrent MB/PNET. Focal
             boost radiotherapy may be delivered prior to immunotherapy if required for local
             control.

          -  Patients receiving any other concurrent anticancer or investigational drug therapy.

          -  Patients with any clinically significant unrelated systemic illness (serious
             infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).

          -  Patients with inability to return for follow-up visits or obtain follow-up studies
             required to assess toxicity to therapy.