Clinical Trial Finder

Inclusion Criteria:

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. .

Exclusion Criteria:

Patients who cannot swallow indoximod pills are excluded. Patients previously treated with indoximod are excluded. Patients with DIPG who have been treated with any prior radiation or medical therapy are excluded. Midline glioma that does not include significant brain stem involvement is not considered DIPG for enrollment purposes, and is excluded. 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. Pregnant women are excluded

Disease-specific Cohorts : Cohort 1A, 1B: progressive glioblastoma (relapsed or refractory) Cohort 2A, 2B: progressive medulloblastoma (relapsed or refractory) Cohort 3A, 3B, 3C: progressive ependymoma (relapsed or refractory) Cohort 4C: newly-diagnosed DIPG (must have no prior radiation or other therapy) . Radiation (or proton) plan sub-cohorts: Sub-cohort A: for patients not eligible for re-irradiation. Sub-cohort B: for patients who are eligible for partial re-irradiation. Sub-cohort C: for patients who are eligible for full-dose radiation (All newly diagnosed DIPG patients and some relapsed ependymoma patients)

Arms

Experimental: Core Regimen, sub-cohort A

For patients not eligible for re-irradiation; Start with Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).

Experimental: Core Regimen, sub-cohort B

For patients who are eligible for partial re-irradiation; Start with indoximod plus up-front re-irradiation, using a palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included); Followed by Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).

Experimental: Core Regimen, sub-cohort C

For patients who are eligible for full-dose radiation; (All newly diagnosed DIPG patients and some relapsed ependymoma patients); Start with indoximod plus up-front radiation, using a palliative full-dose radiation plan to all known sites of disease (>50 Gy to brain, >45 Gy to spine); Followed by Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).

Experimental: Salvage Regimen 1

For patients who wish to continue access to indoximod after progression on the Core Regimen; Cross-over to indoximod with oral metronomic cyclophosphamide and etoposide).

Experimental: Salvage Regimen 2

For patients who wish to continue access to indoximod after progression on the Core Regimen; Cross-over to indoximod with oral lomustine and temozolomide).

Interventions

Drug: - Indoximod

Indoximod will be taken by mouth twice daily during radiation and throughout each chemo-immunotherapy treatment cycle.

Radiation: - Partial Radiation

Palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included).

Radiation: - Full-dose Radiation

Palliative full-dose radiation plan to all known sites of disease (>50 Gy to brain, >45 Gy to spine).

Drug: - Temozolomide

Temozolomide will be taken by mouth once daily, on days 1-5 of each chemo-immunotherapy treatment cycle.

Drug: - Cyclophosphamide

Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each chemo-immunotherapy treatment cycle.

Drug: - Etoposide

Etoposide will be taken by mouth once daily, on days 1-21 of each chemo-immunotherapy treatment cycle.

Drug: - Lomustine

Lomustine will be taken by mouth once daily, on day 1 of each chemo-immunotherapy treatment cycle.