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

Launched by THEODORE S. JOHNSON · Oct 22, 2021

Keywords

ClinConnect Summary

The clinical trial titled "Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer" is exploring a new treatment approach for children and young adults aged 6 to 25 who have specific types of brain cancer, such as ependymoma, medulloblastoma, and glioblastoma. The goal of the study is to find the safest dose of a drug called ibrutinib, when used together with indoximod and other chemotherapy medications, to see if this combination can help boost the body’s immune response against the cancer. Participants will receive four different medications and will be monitored closely for any side effects or improvement in their condition.

To be eligible for this trial, patients must have had their cancer return or not respond to previous treatments and need to have a confirmed diagnosis through imaging tests. Additionally, they must be able to swallow pills and meet certain health criteria, like having good kidney and liver function. Participants will be required to understand the study and provide consent, and they will be closely followed by doctors throughout the process. This trial is currently recruiting participants, offering a potential new option for those who have run out of standard treatment choices.

Gender

ALL

Eligibility criteria

• 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.
• • .
• Exclusion Criteria:
• • 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.