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

Cancer Type
Brain & Spinal Cord Tumor
Trial Phase
Phase II
3 - 21 Years, Male and Female
Study Type
Protocol IDs
GCC1949 (primary)
Study Sponsor
Theodore S. Johnson


Indoximod was developed to inhibit the IDO (indoleamine 2,3-dioxygenase) enzymatic pathway,
which is important in the natural regulation of immune responses. This potent immune
suppressive mechanism has been implicated in regulating immune responses in settings as
diverse as infection, tissue/organ transplant, autoimmunity, and cancer. By inhibiting the
IDO pathway, we hypothesize that indoximod will improve antitumor immune responses and
thereby slow the growth of tumors.

The central clinical hypothesis for the GCC1949 study is that inhibiting the pivotal IDO
pathway by adding indoximod immunotherapy during chemotherapy and/or radiation is a potent
approach for breaking immune tolerance to pediatric tumors that will improve outcomes,
relative to standard therapy alone.

This is an NCI-funded (R01 CA229646, MPI: Johnson and Munn) open-label phase 2 trial using
indoximod-based combination chemo-radio-immunotherapy for treatment of patients age 3 to 21
years who have progressive brain cancer (glioblastoma, medulloblastoma, or ependymoma), or
newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Statistical analysis will stratify
patients based on whether their treatment plan includes up-front radiation (or proton)
therapy in combination with indoximod. Central review of tissue diagnosis from prior surgery
is required, except non-biopsied DIPG. This study will use the "immune-adapted Response
Assessment for Neuro-Oncology" (iRANO) criteria for measurement of outcomes. Planned
enrollment is up to 140 patients.


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)


  1. 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

Treatment Sites in Georgia

Aflac Cancer and Blood Disorders Center of Children’s at Egleston

1405 Clifton Road NE
3rd Floor
Atlanta, GA 30322

Augusta University Medical Center

1120 15th Street
Augusta, GA 30912

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