NCT05106296

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

Recruiting now Phase 1 Last updated 9 January 2026

What this trial tests

Phase 1 trial testing Indoximod in Ependymoma in 37 participants. Currently enrolling.

Timeline

8 February 2022

Primary endpoint
30 March 2028

30 September 2028

Quick facts

Lead sponsor	Theodore S. Johnson
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	37
Start date	8 February 2022
Primary completion	30 March 2028
Estimated completion	30 September 2028
Sites	1 location across United States

Drugs / interventions tested

• Indoximod
• Ibrutinib (ibrutinib) — full drug profile →
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Etoposide (etoposide) — full drug profile →
• Ibrutinib (ibrutinib) — full drug profile →
• Temozolomide (temozolomide) — full drug profile →

Conditions studied

• Ependymoma — all drugs for Ependymoma →
• Medulloblastoma — all drugs for Medulloblastoma →
• Glioblastoma — all drugs for Glioblastoma →
• Primary Brain Tumor — all drugs for Primary Brain Tumor →

Sponsor

Theodore S. Johnson

Who can join

Adults 3 to 25, any sex, with Ependymoma or Medulloblastoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Molecular mechanisms and therapeutic significance of Tryptophan Metabolism and signaling in cancer.
   Yan J, Chen D, Ye Z, Zhu X, et al · · 2024 · cited 91× · PMID 39472902 · DOI 10.1186/s12943-024-02164-y
2. Targeting Indoleamine Dioxygenase and Tryptophan Dioxygenase in Cancer Immunotherapy: Clinical Progress and Challenges.
   Peng X, Zhao Z, Liu L, Bai L, et al · · 2022 · cited 38× · PMID 35965963 · DOI 10.2147/dddt.s373780
3. Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial.
   Johnson TS, MacDonald TJ, Pacholczyk R, Aguilera D, et al · · 2024 · cited 32× · PMID 37715730 · DOI 10.1093/neuonc/noad174
4. The immunosuppressive role of indoleamine 2, 3-dioxygenase in glioblastoma: mechanism of action and immunotherapeutic strategies.
   Hosseinalizadeh H, Mahmoodpour M, Samadani AA, Roudkenar MH. · · 2022 · cited 31× · PMID 35716323 · DOI 10.1007/s12032-022-01724-w
5. Tryptophan Metabolism Disorder-Triggered Diseases, Mechanisms, and Therapeutic Strategies: A Scientometric Review.
   Chen X, Xu D, Yu J, Song XJ, et al · · 2024 · cited 26× · PMID 39408347 · DOI 10.3390/nu16193380
6. Ibrutinib in the Treatment of Solid Tumors: Current State of Knowledge and Future Directions.
   Szklener K, Michalski A, Żak K, Piwoński M, et al · · 2022 · cited 21× · PMID 35456016 · DOI 10.3390/cells11081338
7. The Tumor Microenvironment of Medulloblastoma: An Intricate Multicellular Network with Therapeutic Potential.
   van Bree NFHN, Wilhelm M. · · 2022 · cited 18× · PMID 36291792 · DOI 10.3390/cancers14205009
8. The Metabolic Orchestration of Immune Evasion in Glioblastoma: From Molecular Perspectives to Therapeutic Vulnerabilities.
   Medikonda R, Abikenari M, Schonfeld E, Lim M. · · 2025 · cited 17× · PMID 40507361 · DOI 10.3390/cancers17111881