RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood 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. 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.

Official Title

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

Quick Facts

Study Start:2022-02-08

Study Completion:2028-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05106296

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.

Ages Eligible for Study:3 Years to 25 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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.).

Inclusion Criteria

Exclusion 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.).

Contacts and Locations

Study Contact

Theodore S. Johnson, MD, PhD

CONTACT

706-721-4962

thjohnson@augusta.edu

Robin Dobbins, RN

CONTACT

706-721-2154

rdobbins@augusta.edu

Principal Investigator

Theodore S. Johnson, MD, PhD

PRINCIPAL_INVESTIGATOR

Augusta University

Study Locations (Sites)

Augusta University, Georgia Cancer Center

Augusta, Georgia, 30912

United States

Collaborators and Investigators

Sponsor: Theodore S. Johnson

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-02-08

Study Completion Date2028-09-30

Study Record Updates