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

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

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.

Sponsors & Collaborators

• Augusta University

  collaborator OTHER

• CureSearch for Children's Cancer

  collaborator UNKNOWN

• Rally Foundation for Childhood Cancer Research

  collaborator OTHER

• Theodore S. Johnson

  lead OTHER

Principal Investigators

• Theodore S. Johnson, MD, PhD · Augusta University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

3 Years

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-02-08

Primary Completion

2028-03-30

Completion

2028-09-30

FDA Drug

Yes

Countries

• United States

Study Locations