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GlioblastomaPhase 2NCT04049669

Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG

A Phase 2 study testing Indoximod, Partial Radiation and Full-dose Radiation in people with Glioblastoma and Medulloblastoma, run by Theodore S. Johnson at 5 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Indoximod was developed to inhibit the IDO (indoleamine 2,3-dioxygenase) enzymatic pathway, which is important in the natural regulation of immune responses. This potent immune suppressive mechanism has been implicated in regulating immune responses in settings as diverse as infection, tissue/organ transplant… Read more about this study

Who is it for?
Ages 3 to 21 years
Conditions the study is for
Glioblastoma, Medulloblastoma, Ependymoma
What is being tested?
Indoximod, Partial Radiation and Full-dose Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
5 sitesUnited States
Study dates
2 Oct 2019to 11 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Diagnosis:
  • Progressive disease with histologically proven initial diagnosis of glioblastoma, medulloblastoma, or ependymoma; With confirmation of progression by either MRI or CSF analysis; Measureable disease is not required for study entry; Patients with progressive disease must have been previously treated with therapeutic radiation as part of treatment for the initial brain cancer diagnosis or for a prior relapse.
  • Newly diagnosed DIPG (diffuse intrinsic pontine glioma) with no prior therapy (including no prior radiation); Biopsy is not required for DIPG.
  • Central review of tissue diagnosis is required, except non-biopsied DIPG; Archival tumor tissue must be located and available prior to study entry.
  • Patients with metastatic disease are eligible.
  • Lansky or Karnofsky performance status score must be ≥ 50%.
Show all 27Show fewer
  • Adequate renal function: creatinine ≤ 1.5-times upper limit of age-adjusted normal.
  • Adequate liver function:
  • ALT ≤ 5-times upper limit of normal.
  • Total bilirubin ≤ 1.5-times upper limit of normal.
  • Adequate Bone marrow function:
  • Absolute neutrophil count (ANC) ≥ 750/mcL.
  • Platelets ≥ 75,000/mcL (transfusion independent).
  • Hemoglobin ≥ 8 g/dL (transfusion independent).
  • Central nervous system: seizure disorders must be well controlled on antiepileptic medication.
  • Prior therapy
  • DIPG patients must not have been treated with any prior radiation or medical therapy.
  • Patients previously treated with indoximod are excluded.
  • Patients previously treated with any other immunotherapy agent, including other IDO-targeted drugs, are eligible for enrollment.
  • Patients previously treated with chemotherapy drugs included in this protocol are eligible for enrollment.
  • Patients must be 14 days from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions:
  • Temozolomide dosed at or above 150 mg/m2 (allowed, but must be at least 21 days from the last dose of temozolomide).
  • Must be 28 days from administration of antibody-based therapies (e.g., bevacizumab), tumor-directed vaccines, or cellular immune therapies (e.g., T cells, NK cells, etc).
  • Must be 56 days from administration of tumor-directed therapies using infectious agents (e.g., viruses, bacteria, etc).
  • Pregnant women are excluded from this study, where pregnancy is confirmed by a positive urine or serum hCG laboratory test.
  • Patients must be able to swallow pills.
  • .

Who cannot join

  • Patients who cannot swallow indoximod pills are excluded.
  • Patients previously treated with indoximod are excluded.
  • Patients with DIPG who have been treated with any prior radiation or medical therapy are excluded.
  • Midline glioma that does not include significant brain stem involvement is not considered DIPG for enrollment purposes, and is excluded.
  • Patients with active systemic infection requiring treatment, including any HIV infection or toxoplasmosis, are excluded.
  • Patients with active autoimmune disease that requires systemic therapy are excluded.
  • Pregnant women are excluded

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • Augusta University, Georgia Cancer Center

    Augusta, Georgia, 30912

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Emory University, Children's Heathcare of Atlanta

    Druid Hills, Georgia, 30322

  • MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase 2 Trial of Indoximod With Chemotherapy and Radiation for Children With Progressive Brain Tumors or Newly Diagnosed DIPG

Indoximod was developed to inhibit the IDO (indoleamine 2,3-dioxygenase) enzymatic pathway, which is important in the natural regulation of immune responses. This potent immune suppressive mechanism has been implicated in regulating immune responses in settings as diverse as infection, tissue/organ transplant, autoimmunity, and cancer. By inhibiting the IDO pathway, we hypothesize that indoximod will improve antitumor immune responses and thereby slow the growth of tumors.

The central clinical hypothesis for the GCC1949 study is that inhibiting the pivotal IDO pathway by adding indoximod immunotherapy during chemotherapy and/or radiation is a potent approach for breaking immune tolerance to pediatric tumors that will improve outcomes, relative to standard therapy alone.

This is an NCI-funded (R01 CA229646, MPI: Johnson and Munn) open-label phase 2 trial using indoximod-based combination chemo-radio-immunotherapy for treatment of patients age 3 to 21 years who have progressive brain cancer (glioblastoma, medulloblastoma, or ependymoma), or newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Statistical analysis will stratify patients based on whether their treatment plan includes up-front radiation (or proton) therapy in combination with indoximod. Central review of tissue diagnosis from prior surgery is required, except non-biopsied DIPG. This study will use the "immune-adapted Response Assessment for Neuro-Oncology" (iRANO) criteria for measurement of outcomes. Planned enrollment is up to 140 patients.

Read the detailed description

Disease-specific Cohorts :

Cohort 1A, 1B (closed to enrollment): relapsed or refractory glioblastoma

Cohort 2A, 2B: relapsed or refractory medulloblastoma

Cohort 3A, 3B, 3C: relapsed or refractory ependymoma

Cohort 4C (closed to enrollment): newly-diagnosed DIPG (must have no prior radiation or other therapy)

.

Radiation (or proton) plan sub-cohorts:

Sub-cohort A: for patients not eligible for re-irradiation

Sub-cohort B: for patients who are eligible for partial re-irradiation

Sub-cohort C: for patients who are eligible for full-dose radiation (All newly diagnosed DIPG patients and some relapsed ependymoma patients)

Being tested
Indoximod, Partial Radiation, Full-dose Radiation, Temozolomide, Cyclophosphamide
Keywords
IDO, indoleamine 2,3-dioxygenase, indoximod, pediatric, childhood, brain tumor, glioblastoma, medulloblastoma, ependymoma, diffuse intrinsic pontine glioma, DIPG, radiation, temozolomide, cyclophosphamide, etoposide, lomustine, immunotherapy, immune, central nervous system, CNS
Medical subject headings
Glioblastoma, Medulloblastoma, Ependymoma, Diffuse Intrinsic Pontine Glioma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IndoximodDrug

    Indoximod will be taken by mouth twice daily during radiation and throughout each chemo-immunotherapy treatment cycle.

  • Partial RadiationRadiation

    Palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included).

  • Full-dose RadiationRadiation

    Palliative full-dose radiation plan to all known sites of disease (>50 Gy to brain, >45 Gy to spine).

  • TemozolomideDrug

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

  • CyclophosphamideDrug

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

  • EtoposideDrug

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

  • LomustineDrug

    Lomustine will be taken by mouth once daily, on day 1 of each chemo-immunotherapy treatment cycle.

Study groups in NCT04049669
Study groupRoleWhat they receive
Core Regimen, sub-cohort AExperimentalFor patients not eligible for re-irradiation; Start with Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).
Receives: Drug: Indoximod; Drug: Temozolomide
Core Regimen, sub-cohort BExperimentalFor patients who are eligible for partial re-irradiation; Start with indoximod plus up-front re-irradiation, using a palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included); Followed by Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).
Receives: Drug: Indoximod; Radiation: Partial Radiation; Drug: Temozolomide
Core Regimen, sub-cohort CExperimentalFor patients who are eligible for full-dose radiation; (All newly diagnosed DIPG patients and some relapsed ependymoma patients); Start with indoximod plus up-front radiation, using a palliative full-dose radiation plan to all known sites of disease (>50 Gy to brain, >45 Gy to spine); Followed by Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).
Receives: Drug: Indoximod; Radiation: Full-dose Radiation; Drug: Temozolomide
Salvage Regimen 1ExperimentalFor patients who wish to continue access to indoximod after progression on the Core Regimen; Cross-over to indoximod with oral metronomic cyclophosphamide and etoposide).
Receives: Drug: Indoximod; Drug: Cyclophosphamide; Drug: Etoposide
Salvage Regimen 2ExperimentalFor patients who wish to continue access to indoximod after progression on the Core Regimen; Cross-over to indoximod with oral lomustine and temozolomide).
Receives: Drug: Indoximod; Drug: Temozolomide; Drug: Lomustine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 8-month iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria)

    For patients with relapsed glioblastoma, medulloblastoma, or ependymoma.

    Measured: Up to 5 years

  2. 12-month Overall Survival (OS)

    For patients with newly diagnosed DIPG (diffuse intrinsic pontine glioma).

    Measured: Up to 5 years

Secondary outcomes (3)
  1. Median Overall Survival (OS)

    For each disease cohort

    Measured: Up to 5 years

  2. Median iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria)

    For each disease cohort

    Measured: Up to 5 years

  3. Median Time to Regimen Failure (TTRF)

    For each disease cohort

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2019
  2. Study start2 Oct 2019
  3. Primary completion21 Sep 2026
  4. Study completion11 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04049669
Sponsor's protocol ID
GCC1949
Other IDs
R01CA229646
Status last verified
Oct 2026
First submitted
2 Aug 2019
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Johnson 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.

    PubMed 37715730
  • Sharma MD, Pacholczyk R, Shi H, Berrong ZJ, Zakharia Y, Greco A, Chang CS, Eathiraj S, Kennedy E, Cash T, Bollag RJ, Kolhe R, Sadek R, McGaha TL, Rodriguez P, Mandula J, Blazar BR, Johnson TS, Munn DH. Inhibition of the BTK-IDO-mTOR axis promotes differentiation of monocyte-lineage dendritic cells and enhances anti-tumor T cell immunity. Immunity. 2021 Oct 12;54(10):2354-2371.e8. doi: 10.1016/j.immuni.2021.09.005. Epub 2021 Oct 5.

    PubMed 34614413

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Indoximod, Partial Radiation and Full-dose Radiation in people with Glioblastoma and Medulloblastoma, run by Theodore S. Johnson at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

8-month iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria) (time frame: Up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04049669, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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