NCT05106296

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

Repurposing Ibrutinib for Chemo-Immunotherapy in a Phase 1b Study of Ibrutinib With Indoximod Plus Metronomic Cyclophosphamide and Etoposide for Pediatric Patients With Brain Cancer

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 37 (estimated)
• Sponsor: Theodore S. Johnson · Academic / Other
• Sex: All
• Age: 3 Years – 25 Years
• Healthy volunteers: Not accepted

Summary

Recent lab-based discoveries suggest that IDO (indoleamine 2,3-dioxygenase) and BTK (Bruton's tyrosine Kinase) form a closely linked metabolic checkpoint in tumor-associated antigen-presenting cells. The central clinical hypothesis for the GCC2020 study is that combining ibrutinib (BTK-inhibitor) with indoximod (IDO-inhibitor) during chemotherapy will synergistically enhance anti-tumor immune responses, leading to improvement in clinical response with manageable overlapping toxicity. The GCC2020 trial is a prospective open-label phase 1 trial to determine the best safe dose of the BTK-inhibitor ibrutinib to use in combination with previously studied chemo-immunotherapy regimens comprised of the investigational IDO-inhibitor indoximod plus oral palliative chemotherapy for participants, age 6 to 25 years, with relapsed or refractory primary brain cancer. Those previously treated with indoximod-based therapy may be eligible, including prior treatment via the phase 2 indoximod study (GCC1949, NCT04049669), the now closed phase 1 study (NLG2105, NCT02502708), or any expanded access (compassionate use) protocols. Ibrutinib will be combined with either indoximod plus oral cyclophosphamide and etoposide (Regimen A) or indoximod plus oral temozolomide (Regimen B). No cross-over between these two regimens will be allowed. Dose-escalation cohorts will determine the best safe dose of ibrutinib for each of these regimens. This will be followed by expansion cohorts, using ibrutinib at the best safe dose for each regimen, to allow assessment of preliminary evidence of efficacy.

Conditions

• Ependymoma
• Medulloblastoma
• Glioblastoma
• Primary Brain Tumor

Interventions

Type	Name	Description
DRUG	Indoximod	Indoximod will be taken by mouth twice daily, throughout each treatment cycle.
DRUG	Ibrutinib	For Regimen A, Ibrutinib will be taken by mouth once daily, on days 1-21 of each treatment cycle.
DRUG	Cyclophosphamide	Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each treatment cycle.
DRUG	Etoposide	Etoposide will be taken by mouth once daily, on days 1-21 of each treatment cycle.
DRUG	Ibrutinib	For Regimen B, Ibrutinib will be taken by mouth once daily, on days 1-14 of each treatment cycle.
DRUG	Temozolomide	Temozolomide will be taken by mouth once daily, on days 1-5 of each treatment cycle.

Timeline

• Start date: 2022-02-08
• Primary completion: 2028-03-30
• Completion: 2028-09-30
• First posted: 2021-11-03
• Last updated: 2026-01-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study