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

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. 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 6 to 25 years, with relapsed or refractory primary brain cancer. Those previously treated with indoximod plus temozolomide 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. 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.

Conditions

Ependymoma, Medulloblastoma, Glioblastoma, Primary Brain Tumor

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Study Overview

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Study Details

Study overview

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 6 to 25 years, with relapsed or refractory primary brain cancer. Those previously treated with indoximod plus temozolomide 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. 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.

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

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

Condition
Ependymoma
Intervention / Treatment

-

Contacts and Locations

Augusta

Augusta University, Georgia Cancer Center, Augusta, Georgia, United States, 30912

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Patients must have prior documented progressive or refractory disease with histologically proven initial diagnosis of ependymoma, medulloblastoma, glioblastoma, or another type of primary cancer of the central nervous system with no curative conventional therapy options available.
  • * Metastatic disease is acceptable.
  • * Patients must have MRI confirmation (with and without gadolinium contrast) of current active disease.
  • * Creatinine clearance (CLcr) \> 25 mL/min (by calculated methods) AND Creatinine ≤ 1.5-times upper limit of age-adjusted normal for age of patient.
  • * Alanine aminotransferase (ALT) ≤ 3-times upper limit of normal.
  • * Aspartate aminotransferase (AST) ≤ 3-times upper limit of normal.
  • * Total bilirubin ≤ 1.5-times upper limit of normal unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
  • * Absolute neutrophil count (ANC) ≥ 1000/mm3 (independent of growth factor support).
  • * Platelets ≥ 100,000/mm3 (independent of transfusion support).
  • * Hemoglobin ≥ 8 g/dL (independent of transfusion support).
  • * Patients previously treated with chemotherapy drugs included in this protocol are eligible for enrollment.
  • * At the time of Screening, patients must be at least 21 days from the administration of any investigational agent (other than indoximod) or prior cytotoxic therapy (including chemotherapy).
  • * At the time of Screening, patients must be at least 28 days from administration of antibody-based therapies (e.g., bevacizumab), tumor-directed vaccines, or cellular immune therapies (e.g., T cells, NK cells, etc.).
  • * At the time of Screening, patients must be at least 56 days from administration of tumor-directed therapies using infectious agents (e.g., viruses, bacteria, etc.).
  • * At the time of Screening, patients must be at least 90 days from any radiation or proton therapy (all modalities, including radiosurgery) that targeted all sites of known disease.
  • * There is no lock-out window for patients who were treated with focal radiation or focal proton therapy (all modalities, including radiosurgery) that did not target all disease sites, if at least one site of active tumor is expected to persist and/or grow.
  • * No investigational or commercial agents, including intrathecal drugs, other than that described by this clinical study protocol (GCC2020) may be administered with the intent to treat the patient's malignancy while they remain enrolled on this study.
  • * Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study. Men must agree to not donate sperm during and for 3 months after the study.
  • * Women who are pregnant or breastfeeding are ineligible for this study.
  • * Patients who become pregnant while participating in this study will have to stop Study Therapy.
  • * Allergies, allergic conditions, and reactive inflammatory conditions that are not autoimmune in nature would not exclude patients (e.g., eczema, asthma, etc.).

Ages Eligible for Study

6 Years to 25 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Theodore S. Johnson,

Theodore S. Johnson, MD, PhD, PRINCIPAL_INVESTIGATOR, Augusta University

Study Record Dates

2026-09