Active — Not RecruitingPhase 2

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

United States130 participantsStarted 2019-10-02

Plain-language summary

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.

Who can participate

Age range3 Years – 21 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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. * Patien…

What they're measuring

8-month iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria)

Timeframe: Up to 5 years

12-month Overall Survival (OS)

Timeframe: Up to 5 years

Trial details

NCT IDNCT04049669

SponsorTheodore S. Johnson

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-08-02