Clinical trial · Interventional
Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients With Progressive Primary Malignant Brain Tumors
A Phase I Trial of Indoximod and Temozolomide-Based Therapy for Children With Progressive Primary Brain Tumors
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (8)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Diffuse Intrinsic Pontine Glioma | Diffuse Intrinsic Pontine Glioma | ONTOLOGY_EXACT | 0.98 |
| Ependymoma | Ependymoma | ONTOLOGY_EXACT | 0.90 |
| Glioblastoma Multiforme | Glioblastoma | CURATED_BROADER | 0.80 |
| Glioma | Glioma | ONTOLOGY_EXACT | 0.98 |
| Gliosarcoma | Gliosarcoma | ONTOLOGY_EXACT | 0.90 |
| Malignant Brain Tumor | Malignant Brain Neoplasm | ALIAS | 0.90 |
| Medulloblastoma | Medulloblastoma | CURATED_BROADER | 0.80 |
| Primary CNS Tumor | Brain Neoplasm | PROBABILISTIC |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Conformal Radiation | Radiation | — | UNRESOLVED |
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Etoposide | Drug | Etoposide | ALIAS |
| Indoximod | Drug | — | UNRESOLVED |
| Temozolomide | Drug | Temozolomide | ALIAS |
Design
Arms and outcomes
Arms (5)
- type
- EXPERIMENTAL
- label
- Group 1 (CLOSED)
- description
- 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
- interventionNames
- Drug: Indoximod
- Drug: Temozolomide
- type
- EXPERIMENTAL
- label
- Group 2 (CLOSED)
- description
- 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
- interventionNames
- Drug: Indoximod
- Drug: Temozolomide
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 3 Years
- Maximum age
- 21 Years
Show eligibility criteria text
Eligibility Criteria * Age: 3-21 years. * Group 1 or Group 3: histologically proven initial diagnosis of primary malignant brain tumor, with no known curative treatment options. * Group 2: histologically proven initial diagnosis of high-grade glioma (WHO grade III and IV), ependymoma, medulloblastoma, or other primary central nervous system tumor. * Group 3b: Patients with a radiographic diagnosis or histologically proven diagnosis of diffuse intrinsic pontine glioma (DIPG). * MRI confirmation of tumor progression or regrowth. * Patients must be able to swallow whole capsules. * Patients with metastatic disease are eligible for enrollment. * 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
References
Publications (1)
- DERIVEDJohnson TS, MacDonald TJ, Pacholczyk R, Aguilera D, Al-Basheer A, Bajaj M, Bandopadhayay P, Berrong Z, Bouffet E, Castellino RC, Dorris K, Eaton BR, Esiashvili N, Fangusaro JR, Foreman N, Fridlyand D, Giller C, Heger IM, Huang C, Kadom N, Kennedy EP, Manoharan N, Martin W, McDonough C, Parker RS, Ramaswamy V, Ring E, Rojiani A, Sadek RF, Satpathy S, Schniederjan M, Smith A, Smith C, Thomas BE, Vaizer R, Yeo KK, Bhasin MK, Munn DH. Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial. Neuro Oncol. 2024 Feb 2;26(2):348-361. doi: 10.1093/neuonc/noad174. PMID 37715730