Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients With Progressive Primary Malignant Brain Tumors

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

81 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2020-02-28

Brief Summary

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This is a first-in-children phase 1 trial using indoximod, an inhibitor of the immune "checkpoint" pathway indoleamine 2,3-dioxygenase (IDO), in combination with temozolomide-based therapy to treat pediatric brain tumors. Using a preclinical glioblastoma model, it was recently shown that adding IDO-blocking drugs to temozolomide plus radiation significantly enhanced survival by driving a vigorous, tumordirected inflammatory response. This data provided the rationale for the companion adult phase 1 trial using indoximod (IND#120813) plus temozolomide to treat adults with glioblastoma, which is currently open (NCT02052648). The goal of this pediatric study is to bring IDO-based immunotherapy into the clinic for children with brain tumors. This study will provide a foundation for future pediatric trials testing indoximod combined with radiation and temozolomide in the up-front setting for patients with newly diagnosed central nervous system tumors.

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Detailed Description

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Conditions

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Glioblastoma Multiforme Glioma Gliosarcoma Malignant Brain Tumor Ependymoma Medulloblastoma Diffuse Intrinsic Pontine Glioma Primary CNS Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1 (CLOSED)

Core Regimen: Dose-escalation of indoximod, in combination with temozolomide, for pediatric patients with progressive brain tumors.

Indoximod will be administered in escalating doses. Initial dosing will be 12.8 mg/kg/dose BID with escalation planned to 22.4 mg/kg/dose BID.

Temozolomide to be given at 200 mg/m\^2 x 5 days

Group Type EXPERIMENTAL

Indoximod

Intervention Type DRUG

Indoximod will be administered orally twice daily.

Temozolomide

Intervention Type DRUG

Temozolomide will be administered on days 1-5 of every 28 day cycle.

Group 2 (CLOSED)

Expansion cohorts: Indoximod therapy at the pediatric recommended phase 2 dose (RP2D) determined by Group 1, in combination with temozolomide.

Indoximod will be administered at the RP2D of 19.2 mg/kg/dose BID.

Temozolomide to be given at 200 mg/m\^2 x 5 days

Group Type EXPERIMENTAL

Indoximod

Intervention Type DRUG

Indoximod will be administered orally twice daily.

Temozolomide

Intervention Type DRUG

Temozolomide will be administered on days 1-5 of every 28 day cycle.

Group 3 (CLOSED)

Dose-escalation of indoximod, in combination with up-front conformal radiation therapy, for pediatric patients with progressive brain tumors.

Indoximod will be administered in escalating doses. Initial dosing will be 12.8 mg/kg/dose BID with escalation planned to 22.4 mg/kg/dose BID.

Temozolomide to be given at 200 mg/m\^2 x 5 days

Group Type EXPERIMENTAL

Indoximod

Intervention Type DRUG

Indoximod will be administered orally twice daily.

Temozolomide

Intervention Type DRUG

Temozolomide will be administered on days 1-5 of every 28 day cycle.

Conformal Radiation

Intervention Type RADIATION

Conformal radiation will be administered on days 3-7 of induction cycle.

Group 3b

Indoximod, in combination with up-front conformal radiation therapy, for pediatric patients with newly diagnosed treatment-naive diffuse intrinsic pontine glioma (DIPG).

Indoximod will be administered at the RP2D of 19.2 mg/kg/dose BID.

Temozolomide to be given at 200 mg/m\^2 x 5 days

Group Type EXPERIMENTAL

Indoximod

Intervention Type DRUG

Indoximod will be administered orally twice daily.

Temozolomide

Intervention Type DRUG

Temozolomide will be administered on days 1-5 of every 28 day cycle.

Conformal Radiation

Intervention Type RADIATION

Conformal radiation will be administered on days 3-7 of induction cycle.

Group 4

Continued access to indoximod in combination with low-dose oral cyclophosphamide and etoposide for patients with progressive disease after treatment with indoximod plus temozolomide.

Indoximod will be administered at 32 mg/kg/dose divided twice daily.

Cyclophosphamide to be given at 2.5 mg/kg/dose daily

Etoposide to be given at 50 mg/m2/dose daily

Group Type EXPERIMENTAL

Indoximod

Intervention Type DRUG

Indoximod will be administered orally twice daily.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be administered orally daily.

Etoposide

Intervention Type DRUG

Etoposide will be administered orally daily.

Interventions

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Indoximod

Indoximod will be administered orally twice daily.

Intervention Type DRUG

Temozolomide

Temozolomide will be administered on days 1-5 of every 28 day cycle.

Intervention Type DRUG

Conformal Radiation

Conformal radiation will be administered on days 3-7 of induction cycle.

Intervention Type RADIATION

Cyclophosphamide

Cyclophosphamide will be administered orally daily.

Intervention Type DRUG

Etoposide

Etoposide will be administered orally daily.

Intervention Type DRUG

Other Intervention Names

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1-methyl-D-tryptophan D-1MT Temodar Methazolastone

Eligibility Criteria

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Inclusion Criteria

* Lansky or Karnofsky performance status score must be \> 50%.
* Seizure disorders must be well controlled on antiepileptic medication.
* DIPG patients enrolled to Group 3b must not have been previously treated with radiation or any medical therapy.
* Patients previously treated with temozolomide, cyclophosphamide, and/or etoposide are eligible for enrollment.

Exclusion Criteria

* Prior invasive malignancy, other than the primary central nervous system tumor, unless the patient has been disease free and off therapy for that disease for a minimum of 3 years
* Patients with baseline QTc interval of more than 470 msec at study entry, and patients with congenital long QTc syndrome.
* Active autoimmune disease

Minimum Eligible Age

3 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No