Evidence map›Paper›PMID 37715730›Full record

ArticleNeuro-oncology2024

Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial.

Theodore S Johnson, Tobey J MacDonald, Rafal Pacholczyk, Dolly Aguilera, Ahmad Al-Basheer, Manish Bajaj, Pratiti Bandopadhayay, Zuzana Berrong, Eric Bouffet, Robert C Castellino and 28 more

3 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
11.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02502708 phase1completednot on this map

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

TypeinterventionalSponsorNewLink Genetics CorporationRan2015 to 2020Enrolled81ConditionsGlioblastoma Multiforme, Glioma, Gliosarcoma, Malignant Brain TumorArmsIndoximod, Temozolomide, Conformal Radiation, Cyclophosphamide, Etoposide
NCT04049669 phase2active not recruitingnot on this map

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

TypeinterventionalSponsorTheodore S. JohnsonRan2019 to 2027Enrolled130ConditionsGlioblastoma, Medulloblastoma, Ependymoma, Diffuse Intrinsic Pontine GliomaArmsIndoximod, Partial Radiation, Full-dose Radiation, Temozolomide, Cyclophosphamide
NCT05106296 phase1recruitingnot on this map

Repurposing Ibrutinib for Chemo-Immunotherapy in a Phase 1b Study of Ibrutinib With Indoximod Plus Metronomic Cyclophosphamide and Etoposide for Pediatric Patients With Brain Cancer

TypeinterventionalSponsorTheodore S. JohnsonRan2022 to 2028Enrolled37ConditionsEpendymoma, Medulloblastoma, Glioblastoma, Primary Brain TumorArmsIndoximod, Ibrutinib, Cyclophosphamide, Etoposide, Temozolomide
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.

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  5. Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors at 8 institutions in 2 countries.

Theodore S JohnsonGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Tobey J MacDonaldAflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
Rafal PacholczykDana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.
Dolly AguileraAflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
Ahmad Al-BasheerGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Manish BajajDepartment of Radiology, Augusta University, Augusta, Georgia, USA.
Pratiti BandopadhayayORCID 0000-0002-4175-4760
Zuzana BerrongGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Eric BouffetDepartment of Paediatrics, The Hospital for Sick Children, Toronto, Canada.ORCID 0000-0002-6832-6539
Robert C CastellinoAflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
Kathleen DorrisDepartment of Pediatrics, Children's Hospital Colorado, Aurora, Colorado, USA.ORCID 0000-0003-0753-2176
Bree R EatonDepartment of Radiation Oncology and Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.
Natia EsiashviliDepartment of Radiation Oncology and Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.
Jason R FangusaroAflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
Nicholas ForemanDepartment of Pediatrics, Children's Hospital Colorado, Aurora, Colorado, USA.
Diana FridlyandDepartment of Pediatrics, Augusta University, Augusta, Georgia, USA.
Cole GillerDepartment of Neurosurgery, Augusta University, Augusta, Georgia, USA.
Ian M HegerDepartment of Neurosurgery, Augusta University, Augusta, Georgia, USA.
Chenbin HuangDepartment of Pediatrics, Emory University, Atlanta, Georgia, USA.
Nadja KadomDepartment of Radiology and Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.
Eugene P KennedyLumos Pharma, Inc. (formerly NewLink Genetics Corporation), Austin, Texas, USA.
Neevika ManoharanDana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.
William MartinDepartment of Radiation Oncology, Augusta University, Augusta, Georgia, USA.
Colleen McDonoughGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Rebecca S ParkerGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Vijay RamaswamyDepartment of Paediatrics, The Hospital for Sick Children, Toronto, Canada.ORCID 0000-0002-6557-895X
Eric RingGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Amyn RojianiGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Ramses F SadekGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Sarthak SatpathyDepartment of Pediatrics, Emory University, Atlanta, Georgia, USA.
Matthew SchniederjanChildren's Healthcare of Atlanta and Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Amy SmithDepartment of Pediatrics, Arnold Palmer Hospital for Children, Orlando, Florida, USA.
Christopher SmithLumos Pharma, Inc. (formerly NewLink Genetics Corporation), Austin, Texas, USA.
Beena E ThomasDepartment of Pediatrics, Emory University, Atlanta, Georgia, USA.
Rachel VaizerDepartment of Pediatrics, Augusta University, Augusta, Georgia, USA.
Kee Kiat YeoDana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.ORCID 0000-0003-0713-6384
Manoj K BhasinAflac Cancer & Blood Disorders Center at Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
David H MunnGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Emory University · USAugusta University · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USAugusta University Health · USChildren's Hospital Colorado · USHospital for Sick Children · CANewLink Genetics (United States) · USArnold Palmer Hospital for Children · US

Funding

Reprogramming the TME for immunogenic antigen-presentationR01CA103320 · NCI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MUNN, DAVID H. · 2003 to 2024
$6.0M
Chemo-radio immunotherapy for pediatric brain tumorsR01CA229646 · NCI · AUGUSTA UNIVERSITY · PI JOHNSON, THEODORE S, MUNN, DAVID H. · 2019 to 2023
$2.9M
Alex's Lemonade Stand FoundationCannonball Kids' cancer FoundationEli's Block Party Childhood Cancer FoundationHyundai Hope on Wheels FoundationLumos Pharma, Inc.Miriam Lloyd Halsey FoundationNCI NIH HHS R01 CA103320NCI NIH HHS R01 CA229646Northern Nevada Children's Cancer FoundationPress On FoundationTrial Blazers for Kids Foundation
6 · The paper itself

Abstract

backgroundRecurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy.

methodsWe conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing.

resultsEighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39-77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2-62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7-29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4-61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2-62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype.

conclusionsIndoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors.

Indexed as

Brain NeoplasmsBrain Stem NeoplasmsChildHumansImmunologic FactorsImmunotherapyTemozolomideTryptophan1-methyltryptophanImmunologic FactorsTemozolomideTryptophanbrain cancerIDOimmunotherapyindoximodpediatric

Identifiers

PMID37715730
PMCPMC10836763
OpenAlexW4386800579

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.