Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer
Status:
Not yet recruiting
Trial end date:
2025-04-01
Target enrollment:
Participant gender:
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.
GCC2020 is a prospective open-label phase 1 trial to determine the best safe dose of
ibrutinib to use in combination with a previously studied chemo-immunotherapy regimen,
comprised of the IDO-inhibitor indoximod plus oral metronomic cyclophosphamide and etoposide
(4-drug combination) for participants, age 12 to 25 years, with relapsed or refractory
ependymoma, medulloblastoma/PNET, or glioblastoma that progressed after previous treatment
with indoximod plus temozolomide. Those previously treated with indoximod plus temozolomide
are eligible, including prior treatment via the on-going phase 2 indoximod study (GCC1949,
NCT04049669), the now closed phase 1 study (NLG2105, NCT02502708), or expanded access
protocols. A dose-escalation cohort will determine the best safe dose of ibrutinib for the
4-drug combination. This will be followed by an expansion cohort, using ibrutinib at the best
safe dose in the 4-drug combination, to allow assessment of preliminary evidence of efficacy.