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Glioblastoma MultiformePhase 1NCT02502708

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

A Phase 1 study testing Indoximod, Temozolomide and Conformal Radiation in people with Glioblastoma Multiforme and Glioma, run by NewLink Genetics Corporation at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 3 to 21 years
Conditions the study is for
Glioblastoma Multiforme, Glioma, Gliosarcoma
What is being tested?
Indoximod, Temozolomide and Conformal Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
5 sitesUnited States
Study dates
Oct 2015to 28 Feb 2020
Phase
Phase 1
Are there results?
None posted in the registry

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

None listed.

Who cannot join

  • 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 locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Children's Heathcare of Atlanta

    Atlanta, Georgia, 30342

  • Augusta University

    Augusta, Georgia, 30912

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Children's Hospitals and Clinics of Minnesota

    Minneapolis, Minnesota, 55404

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

Other trials in United States

About this study

Official title: A Phase I Trial of Indoximod and Temozolomide-Based Therapy for Children With Progressive Primary Brain Tumors

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.

Being tested
Indoximod, Temozolomide, Conformal Radiation, Cyclophosphamide, Etoposide
Keywords
glioblastoma multiforme, glioma, gliosarcoma, malignant brain tumor, ependymoma, medulloblastoma
Medical subject headings
Glioblastoma, Glioma, Gliosarcoma, Brain Neoplasms, Ependymoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma

What participants receive

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

  • IndoximodDrug

    Also called 1-methyl-D-tryptophan, D-1MT

    Indoximod will be administered orally twice daily.

  • TemozolomideDrug

    Also called Temodar, Methazolastone

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

  • Conformal RadiationRadiation

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

  • CyclophosphamideDrug

    Cyclophosphamide will be administered orally daily.

  • EtoposideDrug

    Etoposide will be administered orally daily.

Study groups in NCT02502708
Study groupRoleWhat they receive
Group 1 (CLOSED)ExperimentalCore 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
Receives: Drug: Indoximod; Drug: Temozolomide
Group 2 (CLOSED)ExperimentalExpansion 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
Receives: Drug: Indoximod; Drug: Temozolomide
Group 3 (CLOSED)ExperimentalDose-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
Receives: Drug: Indoximod; Drug: Temozolomide; Radiation: Conformal Radiation
Group 3bExperimentalIndoximod, 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
Receives: Drug: Indoximod; Drug: Temozolomide; Radiation: Conformal Radiation
Group 4ExperimentalContinued 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
Receives: Drug: Indoximod; Drug: Cyclophosphamide; Drug: Etoposide

What is being measured

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

  1. Incidence of regimen limiting toxicities (RLTs)

    To estimate the RP2D of indoximod combined with temozolomide

    Measured: First 28 days of treatment

  2. Objective Response Rate

    To assess preliminary evidence of efficacy of indoximod and temozolomide using COG brain tumor measurement criteria.

    Measured: Up to three years

  3. Incidence of regimen limiting toxicities (RLTs)

    To estimate the RP2D of indoximod combined with conformal radiation

    Measured: First 35 days of treatment

  4. Safety and tolerability assessed by development of AEs and laboratory parameters of indoximod in combination with cyclophosphamide and etoposide.

    In patients who initially achieve prolonged stable disease or better with Indoximod plus temozolomide but then develop progressive disease

    Measured: Up to three years

Secondary outcomes (6)

  1. Pharmacokinetics: Serum concentrations (Cmax/Steady State)

    Group 1

    Measured: First 48 hours of treatment

  2. Safety and Tolerability of Indoximod combined with Temozolomide as assessed by incidence and severity of adverse events, dose interruptions and dose reductions.

    Group 1 and 2

    Measured: Continuous during study until 30 days after study treatment is complete.

  3. Progression Free Survival (PFS)

    Group 2

    Measured: Up to three years

  4. Time to Progression

    Group 2

    Measured: Start of study until disease progression follow-up, up to three years

  5. Overall Survival

    Group 2

    Measured: Start of study until end of follow-up, up to five years

  6. Safety and Feasibility of Indoximod combined with conformal radiation as assessed by incidence and severity of adverse events, dose interruptions and dose reductions.

    Group 3

    Measured: Continuous during study until 30 days after study treatment is complete.

Timeline

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

  1. First posted20 Jul 2015 (estimated)
  2. Study startOct 2015
  3. Primary completion12 Dec 2019
  4. Study completion28 Feb 2020

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02502708
Sponsor's protocol ID
NLG2105
Status last verified
Jun 2020
First submitted
6 Jul 2015
Last updated
4 Jun 2020
Results posted
No
Data monitoring committee
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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Indoximod, Temozolomide and Conformal Radiation in people with Glioblastoma Multiforme and Glioma, run by NewLink Genetics Corporation 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 0 inclusion and 3 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: finished, as of the sponsor's last update on 4 Jun 2020. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of regimen limiting toxicities (RLTs) (time frame: First 28 days of treatment). The study lists 4 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 NCT02502708, which also lists 1 linked publication.

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 4 Jun 2020.

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