Phase 1b Study of Ibrutinib and Indoximod Combined with Chemotherapy for Children and Young Adults with Relapsed or Refractory Brain Cancer

What this Trial Is About

Recent discoveries suggest that IDO and BTK enzymes play a linked role in controlling immune responses in tumor-related cells. This trial studies how combining ibrutinib, a BTK inhibitor, with indoximod, an IDO inhibitor, alongside chemotherapy may improve anti-tumor immune activity. The study focuses on children and young adults aged 3 to 25 years with relapsed or refractory primary brain cancers, such as ependymoma, medulloblastoma, and glioblastoma, who have limited treatment options. Participants receive one of two chemotherapy regimens combined with ibrutinib and indoximod. Regimen A includes oral cyclophosphamide and etoposide with ibrutinib taken daily for 21 days per cycle. Regimen B includes oral temozolomide with ibrutinib taken daily for 14 days per cycle. Indoximod is taken twice daily throughout each cycle. The trial begins with dose-escalation to find the safest dose of ibrutinib for each regimen, followed by expansion groups that assess early signs of treatment response. During the study, participants will undergo regular monitoring for side effects and treatment response through clinical assessments and MRI scans. Researchers will measure toxicities during the first 90 days and track objective response rates over up to five years. Additional outcomes include adverse events, treatment delays, dose reductions, progression-free survival, and overall survival. The study lasts for several years to monitor safety and effectiveness of these combinations in pediatric brain cancer.

Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer