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Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
Sponsor: Theodore S. Johnson
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.
Official title: Phase 2 Trial of Indoximod With Chemotherapy and Radiation for Children With Progressive Brain Tumors or Newly Diagnosed DIPG
Key Details
Gender
All
Age Range
3 Years - 21 Years
Study Type
INTERVENTIONAL
Enrollment
130
Start Date
2019-10-02
Completion Date
2027-10-02
Last Updated
2026-01-08
Healthy Volunteers
No
Interventions
Indoximod
Indoximod will be taken by mouth twice daily during radiation and throughout each chemo-immunotherapy treatment cycle.
Partial Radiation
Palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included).
Full-dose Radiation
Palliative full-dose radiation plan to all known sites of disease (\>50 Gy to brain, \>45 Gy to spine).
Temozolomide
Temozolomide will be taken by mouth once daily, on days 1-5 of each chemo-immunotherapy treatment cycle.
Cyclophosphamide
Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each chemo-immunotherapy treatment cycle.
Etoposide
Etoposide will be taken by mouth once daily, on days 1-21 of each chemo-immunotherapy treatment cycle.
Lomustine
Lomustine will be taken by mouth once daily, on day 1 of each chemo-immunotherapy treatment cycle.
Locations (5)
Augusta University, Georgia Cancer Center
Augusta, Georgia, United States
Emory University, Children's Heathcare of Atlanta
Druid Hills, Georgia, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
MD Anderson Cancer Center
Houston, Texas, United States