RecruitingPhase 1

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

United States37 participantsStarted 2022-02-08

Plain-language summary

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.

Who can participate

Age range3 Years – 25 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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, patient…

What they're measuring

Incidence of regimen-limiting toxicity (RLT) for Regimen A

Timeframe: First 90 days of treatment

Objective Response Rate (ORR) for Regimen A

Timeframe: Up to 5 years

Incidence of regimen-limiting toxicity (RLT) for Regimen B

Timeframe: First 90 days of treatment

Objective Response Rate (ORR) for Regimen B

Timeframe: Up to 5 years

Trial details

NCT IDNCT05106296

SponsorTheodore S. Johnson

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2028-03-30

Contact for this trial

Theodore S. Johnson, MD, PhD

706-721-4962 thjohnson@augusta.edu

View on ClinicalTrials.gov More Ependymoma trials

Plain-language summary

Who can participate

Age range3 Years – 25 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Incidence of regimen-limiting toxicity (RLT) for Regimen A

Timeframe: First 90 days of treatment

Objective Response Rate (ORR) for Regimen A

Timeframe: Up to 5 years

Incidence of regimen-limiting toxicity (RLT) for Regimen B

Timeframe: First 90 days of treatment

Objective Response Rate (ORR) for Regimen B

Timeframe: Up to 5 years