PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy

Inclusion Criteria:

• Subjects must have proven pediatric cancer with confirmation at diagnosis or at thetime of recurrence/progression and clinical determination of disease for which thereis no known effective curative therapy or disease that is refractory to establishedproven therapies fitting into one of the following categories:

• Disease Status:

High Risk Neuroblastoma-

1. Patients that have relapsed following standard of care therapy or having progressedduring standard of care therapy and non-responsive/progressive to accepted curativechemotherapy.

2. Neuroblastoma must be age >12 months at enrollment

Diffuse Intrinsic Pontine (or other brain stem) Glioma

1. Newly-diagnosed patients willing to undergo biopsy

2. Must be within 2 months of diagnosis and prior to starting radiation

3. DIPG must be ≥ 3 years of age at enrollment

• All subjects must be age ≤ 30 years at enrollment

• Patient and/or parents/guardian willing to consent to biopsy for obtainingtumor material for confirmatory diagnosis and/or tumor RNA extraction andamplification.

• Subjects must have measurable disease as defined Per section 8 at the time ofbiopsy and tumor or bone marrow must be accessible for biopsy. Tumor or bonemarrow samples submitted for analysis must contain >20% viable tumor tissue toqualify. Note: Subjects with NB who are expected to have no evidence of diseaseafter surgical removal of their tumor are still eligible for this trial iftheir disease would normally require adjuvant chemotherapy treatment aftersurgery despite NED status.

• Current disease state must be one for which there is currently no knowneffective therapy

• Specimens will be obtained only in a non-significant risk manner and not solelyfor the purpose of investigational testing.

• Lansky or Karnofsky Score must be ≥ 60

• Bone Marrow:

1. ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported- >24 hrs off G-CSFand 7 days off neulasta)
2. Platelets ≥ 100,000/µl (can be transfused)
3. Hemoglobin > 8 g/dL (can be transfused)

• Renal: Serum creatinine ≤ upper limit of institutional normal.

• Adequate liver function must be demonstrated, defined as:

1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
2. ALT (SGPT) ≤ 3 times upper limit of normal (ULN) for age
3. AST (SGOT) ≤ 3 times upper limit of normal (ULN) for age.

• Subjects with CNS disease currently taking steroids must have been on a stabledose of steroids for at least one week prior to their biopsy and must not haveprogressive hydrocephalus at enrollment.

• A negative serum pregnancy test is required for female participants ofchildbearing potential (≥13 years of age or after onset of menses)

• Both male and female post-pubertal study subjects need to agree to use one ofthe more effective birth control methods during treatment and for six monthsafter treatment is stopped. These methods include total abstinence (no sex),oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrelimplants (Norplant), or medroxyprogesterone acetate injections (Depo-proverashots). If one of these cannot be used, contraceptive foam with a condom isrecommended.

• Informed Consent: All subjects and/or legal guardians must sign informedwritten consent. Assent, when appropriate, will be obtained according toinstitutional guidelines

• Post-Biopsy: Patients with post-biopsy neurological deficits should havedeficits that are stable for a minimum of 1 week prior to registration.

Exclusion Criteria:

• Absence of tumor on biopsy specimen or a diagnosis other than NBL or glioma onbiopsy

• Known autoimmune or immunosuppressive disease or human immunodeficiency virusinfection.

• Subjects with significant renal, cardiac, pulmonary, hepatic or other organdysfunction.

• Prior allergic reaction to GM-CSF or Td.

• Subjects who have received any cytotoxic chemotherapy within the last 7 days priorto biopsy or focal radiotherapy in the case of patients with diffuse intrinsicpontine (or other brain stem) gliomas

• Subjects with NBL who have received any radiotherapy to the primary sample sitewithin the last 14 days (radiation may be included in treatment decision afterbiopsy).

• Subjects receiving any investigational drug concurrently.

• Subjects with uncontrolled serious infections or a life-threatening illness (unrelated to tumor)

• Subjects with any other medical condition, including malabsorption syndromes, mentalillness or substance abuse, deemed by the Investigator to be likely to interferewith the interpretation of the results or which would interfere with a subject'sability to sign or the legal guardian's ability to sign the informed consent, andsubject's ability to cooperate and participate in the study