A Phase 1 interventional study of Indoximod and Temozolomide in Glioblastoma Multiforme, Glioma and Gliosarcoma, sponsored by NewLink Genetics Corporation. Completed at 5 sites in United States. Open to participants aged 3 Years to 21 Years. Per ClinicalTrials.gov, last updated 2020-06-04.
Sponsored by NewLink Genetics Corporation · Phase 1, Interventional, and Treatment
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.
9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.
This study's enrollment of 81 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →NewLink Genetics Corporation is the lead sponsor of 34 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Eligibility Criteria
Exclusion Criteria
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
Drug: Indoximod · Drug: Temozolomide
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
Drug: Indoximod · Drug: Temozolomide
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
Drug: Indoximod · Drug: Temozolomide · Radiation: Conformal Radiation
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
Drug: Indoximod · Drug: Temozolomide · Radiation: Conformal Radiation
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
Drug: Indoximod · Drug: Cyclophosphamide · Drug: Etoposide
Indoximod will be administered orally twice daily.
Also known as: 1-methyl-D-tryptophan, D-1MT
Temozolomide will be administered on days 1-5 of every 28 day cycle.
Also known as: Temodar, Methazolastone
Conformal radiation will be administered on days 3-7 of induction cycle.
Cyclophosphamide will be administered orally daily.
Etoposide will be administered orally daily.
Incidence of regimen limiting toxicities (RLTs)
To estimate the RP2D of indoximod combined with temozolomide
Time frame: First 28 days of treatment
Objective Response Rate
To assess preliminary evidence of efficacy of indoximod and temozolomide using COG brain tumor measurement criteria.
Time frame: Up to three years
Incidence of regimen limiting toxicities (RLTs)
To estimate the RP2D of indoximod combined with conformal radiation
Time frame: First 35 days of treatment
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
Time frame: Up to three years
Pharmacokinetics: Serum concentrations (Cmax/Steady State)
Group 1
Time frame: First 48 hours of treatment
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
Time frame: Continuous during study until 30 days after study treatment is complete.
Progression Free Survival (PFS)
Group 2
Time frame: Up to three years
Time to Progression
Group 2
Time frame: Start of study until disease progression follow-up, up to three years
Overall Survival
Group 2
Time frame: Start of study until end of follow-up, up to five years
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
Time frame: Continuous during study until 30 days after study treatment is complete.
This study is completed, as verified in Jun 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
NewLink Genetics Corporation