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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 3 Years - 21 Years
Gender All
More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT02502708
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 NewLink Genetics Corporation
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Gene Kennedy, MD
Principal Investigator Affiliation NewLink Genetics Corporation
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Glioblastoma Multiforme, Glioma, Gliosarcoma, Malignant Brain Tumor, Ependymoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma, Primary CNS Tumor
Arms & Interventions

Arms

Experimental: 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

Experimental: 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

Experimental: 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

Experimental: 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

Experimental: 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

Interventions

Drug: - Indoximod

Indoximod will be administered orally twice daily.

Drug: - Temozolomide

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

Radiation: - Conformal Radiation

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

Drug: - Cyclophosphamide

Cyclophosphamide will be administered orally daily.

Drug: - Etoposide

Etoposide will be administered orally daily.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Children's Hospital Colorado, Aurora, Colorado

Status

Address

Children's Hospital Colorado

Aurora, Colorado, 80045

Arnold Palmer Hospital for Children, Orlando, Florida

Status

Address

Arnold Palmer Hospital for Children

Orlando, Florida, 32806

Children's Heathcare of Atlanta, Atlanta, Georgia

Status

Address

Children's Heathcare of Atlanta

Atlanta, Georgia, 30342

Augusta University, Augusta, Georgia

Status

Address

Augusta University

Augusta, Georgia, 30912

Minneapolis, Minnesota

Status

Address

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404

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