Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial.
Theodore S Johnson, Tobey J MacDonald, Rafal Pacholczyk...
https://pubmed.ncbi.nlm.nih.gov/37715730Actively Recruiting
Phase 1
Age: 3Years - 25Years
All Genders
ID05106296
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
Led by Theodore S. Johnson · Updated on 2026-01-09
37
Participants Needed
1
Research Sites
26 weeks
Total Duration
On this page
Sponsors
T
Theodore S. Johnson
Lead Sponsor
A
Augusta University
Collaborating Sponsor
AI-Summary
What this Trial Is About
Recent discoveries suggest that IDO and BTK enzymes play a linked role in controlling immune responses in tumor-related cells. This trial studies how combining ibrutinib, a BTK inhibitor, with indoximod, an IDO inhibitor, alongside chemotherapy may improve anti-tumor immune activity. The study focuses on children and young adults aged 3 to 25 years with relapsed or refractory primary brain cancers, such as ependymoma, medulloblastoma, and glioblastoma, who have limited treatment options. Participants receive one of two chemotherapy regimens combined with ibrutinib and indoximod. Regimen A includes oral cyclophosphamide and etoposide with ibrutinib taken daily for 21 days per cycle. Regimen B includes oral temozolomide with ibrutinib taken daily for 14 days per cycle. Indoximod is taken twice daily throughout each cycle. The trial begins with dose-escalation to find the safest dose of ibrutinib for each regimen, followed by expansion groups that assess early signs of treatment response. During the study, participants will undergo regular monitoring for side effects and treatment response through clinical assessments and MRI scans. Researchers will measure toxicities during the first 90 days and track objective response rates over up to five years. Additional outcomes include adverse events, treatment delays, dose reductions, progression-free survival, and overall survival. The study lasts for several years to monitor safety and effectiveness of these combinations in pediatric brain cancer.
CONDITIONS
Brief Title
Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer
Who Can Participate
Age: 3Years - 25Years
All Genders
Eligibility Criteria
You may qualify if you...
- Diagnosis of relapsed or refractory ependymoma, medulloblastoma, glioblastoma, or other primary central nervous system cancer with no curative options
- Metastatic disease allowed
- MRI confirmation of current active disease
- Ability to swallow pills
- Lansky or Karnofsky performance score of 50% or higher
- Adequate kidney function with creatinine clearance over 25 mL/min and age-adjusted creatinine within limits
- Adequate liver function with ALT and AST under 3 times normal and bilirubin under 1.5 times normal unless due to Gilbert's syndrome or non-liver cause
- Adequate bone marrow function with ANC at least 1000/mm3, platelets at least 100,000/mm3, and hemoglobin at least 8 g/dL
- Well-controlled seizure disorders on medication
- Previously treated with chemotherapy drugs in this protocol allowed
- At least 21 days since prior investigational or cytotoxic therapy (except indoximod)
- At least 28 days since antibody therapies or tumor vaccines
- At least 56 days since infectious agent tumor therapies
- At least 90 days since radiation or proton therapy targeting all known disease sites
- No concurrent anti-cancer therapies besides this protocol
- Use of highly effective birth control during and after study for sexually active participants
- Informed consent signed by patient or parent if under 18
You will not qualify if you...
- Inability to swallow pills
- Known allergy to any study drugs
- Active autoimmune disease requiring systemic therapy (non-autoimmune allergies like eczema or asthma allowed)
- Pregnancy or breastfeeding
- Major surgery or unhealed wound within 4 weeks
- Central nervous system lymphoma
- Active bleeding, recent stroke, or intracranial hemorrhage within 6 months except stable postsurgical blood products
- Need for anticoagulation with warfarin or similar drugs
- Chronic treatment with strong CYP3A inhibitors
- Significant heart disease or recent heart attack within 6 months
- Baseline QTc interval over 470 msec or congenital long QT syndrome
- Recent live vaccine within 4 weeks
- Active HIV, Hepatitis B or C, or uncontrolled infection
- Any other life-threatening condition or organ dysfunction risking safety or study outcomes
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Repeated 28-day cycles for up to 90 days or longer based on treatment response and tolerance
Participants receive chemo-immunotherapy with either Regimen A or Regimen B, involving oral medications taken in cycles of at least 28 days.
Visits occur each treatment cycle for medication administration and monitoring
Follow-up
Duration - Up to 5 years
Participants are monitored for treatment response and safety, including assessments up to 5 years after treatment.
Periodic visits for long-term monitoring and assessments
Trial Site Locations
Total: 1 location
1
Augusta University, Georgia Cancer Center
Augusta, Georgia, United States, 30912
Actively Recruiting
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Research Team
T
Theodore S. Johnson, MD, PhD
R
Robin Dobbins, RN
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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Published Research Related To This Trial
Inhibition of the BTK-IDO-mTOR axis promotes differentiation of monocyte-lineage dendritic cells and enhances anti-tumor T cell immunity.
Madhav D Sharma, Rafal Pacholczyk, Huidong Shi...
https://pubmed.ncbi.nlm.nih.gov/34614413