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

ConditionsEpendymomaMedulloblastomaGlioblastomaPrimary Brain Tumor
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age3-25
SponsorTheodore S. Johnson

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Creatinine clearance (CLcr) > 25 mL/min (by calculated methods) AND Creatinine ≤ 1.5-times upper limit of age-adjusted normal for age of patient.

Disqualifiers

Allergies, allergic conditions, and reactive inflammatory conditions that are not autoimmune in nature would not exclude patients (e.g., eczema, asthma, etc.).

Trial design

Design model

Parallel

Treatments tested in this trial

  • Indoximod

    Drug

    Indoximod will be taken by mouth twice daily, throughout each treatment cycle.

  • Ibrutinib

    Drug

    For Regimen A, Ibrutinib will be taken by mouth once daily, on days 1-21 of each treatment cycle.

  • Cyclophosphamide

    Drug

    Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each treatment cycle.

  • Etoposide

    Drug

    Etoposide will be taken by mouth once daily, on days 1-21 of each treatment cycle.

  • Ibrutinib

    Drug

    For Regimen B, Ibrutinib will be taken by mouth once daily, on days 1-14 of each treatment cycle.

  • Temozolomide

    Drug

    Temozolomide will be taken by mouth once daily, on days 1-5 of each treatment cycle.

Treatment groups

37 Participants
are divided into 2 treatment groups
Group A: Regimen AExperimental treatment 4 interventions
Group B: Regimen BExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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

To determine the pediatric recommended phase 2 dose (RP2D) of ibrutinib, when combined with indoximod-based chemo-immunotherapy (Regimen A)

Time frame
First 90 days of treatment
2

Objective Response Rate (ORR) for Regimen A

Defined as the proportion of patients with a best objective response of either complete response (CR) or partial response (PR), using "immunotherapy Response Assessment for Neuro-Oncology" (iRANO) criteria

Time frame
Up to 5 years
3

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

To determine the pediatric recommended phase 2 dose (RP2D) of ibrutinib, when combined with indoximod-based chemo-immunotherapy (Regimen B)

Time frame
First 90 days of treatment
4

Objective Response Rate (ORR) for Regimen B

Defined as the proportion of patients with a best objective response of either complete response (CR) or partial response (PR), using "immunotherapy Response Assessment for Neuro-Oncology" (iRANO) criteria

Time frame
Up to 5 years

Secondary outcomes

1

Adverse events (AEs)

To assess frequency, severity, and recoverability of AEs for the treatment regimen

Time frame
Up to 19 months
2

Frequency of cycle delays for toxicity

To assess whether the immunotherapy contributes to delays in starting subsequent cycles of the chemotherapy drugs

Time frame
Up to 18 months
3

Frequency of dose-reductions of the chemotherapy regimen

To assess whether the immunotherapy contributes to reductions in the doses of the chemotherapy drugs

Time frame
Up to 18 months
4

Complete Response Rate (CRR)

Defined as the proportion of patients with a best objective response of CR using iRANO criteria

Time frame
Up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Theodore S. Johnson

Lead sponsor

Augusta University

Sponsor institution

Augusta University

Collaborator

CureSearch for Children's Cancer

Collaborator

Rally Foundation for Childhood Cancer Research

Collaborator

Source ClinicalTrials.gov
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