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

Description

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.

Conditions

Glioblastoma, Medulloblastoma, Ependymoma, Diffuse Intrinsic Pontine Glioma

Study Overview

Study Details

Study overview

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.

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

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

Condition
Glioblastoma
Intervention / Treatment

-

Contacts and Locations

Augusta

Augusta University, Georgia Cancer Center, Augusta, Georgia, United States, 30912

Druid Hills

Emory University, Children's Heathcare of Atlanta, Druid Hills, Georgia, United States, 30322

Boston

Dana-Farber Cancer Institute, Boston, Massachusetts, United States, 02215

Cincinnati

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States, 45229

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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.
  • * ALT ≤ 5-times upper limit of normal.
  • * Total bilirubin ≤ 1.5-times upper limit of normal.
  • * Absolute neutrophil count (ANC) ≥ 750/mcL.
  • * Platelets ≥ 75,000/mcL (transfusion independent).
  • * Hemoglobin ≥ 8 g/dL (transfusion independent).
  • * 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.
  • * 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).

Ages Eligible for Study

3 Years to 21 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Theodore S. Johnson,

Theodore S Johnson, MD, PhD, PRINCIPAL_INVESTIGATOR, Augusta University

Study Record Dates

2027-10-02