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

Inclusion Criteria

• •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:
• •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.
• •Contraception, pregnancy, and breastfeeding:
• •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.
• •Patients, or their parent for patients less than 18 years of age, must sign an Informed Consent Document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study.
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