Phase 2 Trial of Indoximod With Chemotherapy and Radiation for Children With Progressive Brain Tumors or Newly Diagnosed DIPG

  • End date
    Oct 2, 2027
  • participants needed
  • sponsor
    Theodore S. Johnson
Updated on 13 October 2022
renal function
medical therapy
karnofsky performance status
initial diagnosis
cytotoxic chemotherapy
experimental drug
progressive disease
neutrophil count
blood transfusion
chemotherapy drugs
glioblastoma multiforme
brain tumor
malignant brain tumor
renal function test
diffuse intrinsic pontine glioma
immunotherapy agent
immunotherapeutic agent


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)

Condition Glioblastoma, Medulloblastoma, Ependymoma, Diffuse Intrinsic Pontine Glioma
Treatment cyclophosphamide, etoposide, Temozolomide, Indoximod, Lomustine, Partial Radiation, Full-dose Radiation
Clinical Study IdentifierNCT04049669
SponsorTheodore S. Johnson
Last Modified on13 October 2022


Yes No Not Sure

Inclusion Criteria

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
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
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)
Patients must be able to swallow pills
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

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
Midline glioma that does not include significant brain stem involvement is not considered
Pregnant women are excluded
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
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