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

Recruiting now · Phase 1

Conditions studied: Ependymoma, Medulloblastoma, Glioblastoma, Primary Brain Tumor

In brief

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.

Key facts

Study ID: NCT05106296
Run by: Theodore S. Johnson
People needed: 37
Starts: 2022-02-08
Expected to finish: 2028-09-30
Last updated by the study team: 2026-01-09

Who can join

Age: 3 and older, up to 25. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Diagnosis:
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.
Patients must be able to swallow pills.
Lansky or Karnofsky performance status score must be ≥ 50%.
Adequate renal function:
Creatinine clearance (CLcr) > 25 mL/min (by calculated methods) AND Creatinine ≤ 1.5-times upper limit of age-adjusted normal for age of patient.
Adequate liver function:
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.
Adequate bone marrow function:
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).
Seizure disorders must be well controlled on antiepileptic medication.
Prior therapy:
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.
Concurrent anti-neoplastic therapy:

You may not qualify if…

Patients who are unable to swallow pills.
Patients with known hypersensitivity to any drugs in the treatment plan.
Patients with active autoimmune disease that requires systemic therapy.
Allergies, allergic conditions, and reactive inflammatory conditions that are not autoimmune in nature would not exclude patients (e.g., eczema, asthma, etc.).
Pregnant or breastfeeding women.
Major surgery or a wound that has not fully healed within 4 weeks of Screening.
Known central nervous system lymphoma.
Patients with active bleeding or history of thrombotic or hemorrhagic stroke, or intracranial hemorrhage, within 6 months prior to Screening; with the exception of retained blood products from recent prior uncomplicated surgery (e.g., tumor biopsy, debulking, or resection; VP shunt placement, etc.).
Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon).
Requires chronic treatment with strong CYP3A inhibitor drugs.
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
Patients with baseline QTc interval of more than 470 msec at the time of Screening, and patients with congenital long QT syndrome.
Vaccinated with live, attenuated vaccines within 4 weeks of Screening.
Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection.
Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib, indoximod, or chemotherapy, or put the study outcomes at undue risk.

Where it is running

Augusta University, Georgia Cancer Center — Augusta, Georgia, United States (enrolling)

Full record on ClinicalTrials.gov

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