Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG

Prior treatment

• Patients previously treated with indoximod are excluded.
• Patients with DIPG who have been treated with any prior radiation or medical therapy are excluded.

Other illness

• Patients with active systemic infection requiring treatment, including any HIV infection or toxoplasmosis, are excluded.
• Patients with active autoimmune disease that requires systemic therapy are excluded.

Other

• Patients who cannot swallow indoximod pills are excluded.
• Midline glioma that does not include significant brain stem involvement is not considered DIPG for enrollment purposes, and is excluded.
• Pregnant women are excluded

• Diagnosis:
• Progressive disease with histologically proven initial diagnosis of glioblastoma, medulloblastoma, or ependymoma; With confirmation of progression by either MRI or CSF analysis; Measureable disease is not required for study entry; Patients with progressive disease must have been previously treated with therapeutic radiation as part of treatment for the initial brain cancer diagnosis or for a prior relapse.
• Newly diagnosed DIPG (diffuse intrinsic pontine glioma) with no prior therapy (including no prior radiation); Biopsy is not required for DIPG.
• Central review of tissue diagnosis is required, except non-biopsied DIPG; Archival tumor tissue must be located and available prior to study entry.
• Patients with metastatic disease are eligible.
  • Lansky or Karnofsky performance status score must be ≥ 50%.
  • Adequate renal function: creatinine ≤ 1.5-times upper limit of age-adjusted normal.
  • Adequate liver function:
• ALT ≤ 5-times upper limit of normal.
• Total bilirubin ≤ 1.5-times upper limit of normal.
  • Adequate Bone marrow function:
• Absolute neutrophil count (ANC) ≥ 750/mcL.
• Platelets ≥ 75,000/mcL (transfusion independent).
• Hemoglobin ≥ 8 g/dL (transfusion independent).
  • Central nervous system: seizure disorders must be well controlled on antiepileptic medication.
  • Prior therapy
• DIPG patients must not have been treated with any prior radiation or medical therapy.
• Patients previously treated with indoximod are excluded.
• Patients previously treated with any other immunotherapy agent, including other IDO-targeted drugs, are eligible for enrollment.
• Patients previously treated with chemotherapy drugs included in this protocol are eligible for enrollment.
  • Patients must be 14 days from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions:
• Temozolomide dosed at or above 150 mg/m2 (allowed, but must be at least 21 days from the last dose of temozolomide).
• Must be 28 days from administration of antibody-based therapies (e.g., bevacizumab), tumor-directed vaccines, or cellular immune therapies (e.g., T cells, NK cells, etc).
• Must be 56 days from administration of tumor-directed therapies using infectious agents (e.g., viruses, bacteria, etc).
  • Pregnant women are excluded from this study, where pregnancy is confirmed by a positive urine or serum hCG laboratory test.
  • Patients must be able to swallow pills.
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