Ignite Creation Date:
2025-12-24 @ 11:02 PM
Ignite Modification Date:
2026-01-01 @ 7:25 AM
Study NCT ID:
NCT04049669
Status:
RECRUITING
Last Update Posted:
2025-07-16
First Post:
2019-08-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005909', 'term': 'Glioblastoma'}, {'id': 'D008527', 'term': 'Medulloblastoma'}, {'id': 'D004806', 'term': 'Ependymoma'}, {'id': 'D000080443', 'term': 'Diffuse Intrinsic Pontine Glioma'}, {'id': 'D001932', 'term': 'Brain Neoplasms'}], 'ancestors': [{'id': 'D001254', 'term': 'Astrocytoma'}, {'id': 'D005910', 'term': 'Glioma'}, {'id': 'D018302', 'term': 'Neoplasms, Neuroepithelial'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D018242', 'term': 'Neuroectodermal Tumors, Primitive'}, {'id': 'D020295', 'term': 'Brain Stem Neoplasms'}, {'id': 'D015192', 'term': 'Infratentorial Neoplasms'}, {'id': 'D016543', 'term': 'Central Nervous System Neoplasms'}, {'id': 'D009423', 'term': 'Nervous System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C525396', 'term': '1-methyltryptophan'}, {'id': 'D000077204', 'term': 'Temozolomide'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}, {'id': 'D005047', 'term': 'Etoposide'}, {'id': 'D008130', 'term': 'Lomustine'}], 'ancestors': [{'id': 'D003606', 'term': 'Dacarbazine'}, {'id': 'D014226', 'term': 'Triazenes'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D011034', 'term': 'Podophyllotoxin'}, {'id': 'D013764', 'term': 'Tetrahydronaphthalenes'}, {'id': 'D009281', 'term': 'Naphthalenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D005960', 'term': 'Glucosides'}, {'id': 'D006027', 'term': 'Glycosides'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D009607', 'term': 'Nitrosourea Compounds'}, {'id': 'D014508', 'term': 'Urea'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009603', 'term': 'Nitroso Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 140}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-10-02', 'type': 'ACTUAL'}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2027-10-02', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-14', 'studyFirstSubmitDate': '2019-08-02', 'studyFirstSubmitQcDate': '2019-08-05', 'lastUpdatePostDateStruct': {'date': '2025-07-16', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-08-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-10-02', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '8-month iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria)', 'timeFrame': 'Up to 5 years', 'description': 'For patients with relapsed glioblastoma, medulloblastoma, or ependymoma.'}, {'measure': '12-month Overall Survival (OS)', 'timeFrame': 'Up to 5 years', 'description': 'For patients with newly diagnosed DIPG (diffuse intrinsic pontine glioma).'}], 'secondaryOutcomes': [{'measure': 'Median Overall Survival (OS)', 'timeFrame': 'Up to 5 years', 'description': 'For each disease cohort'}, {'measure': 'Median iRANO-PFS (Progression-Free Survival, defined by immune-adapted iRANO criteria)', 'timeFrame': 'Up to 5 years', 'description': 'For each disease cohort'}, {'measure': 'Median Time to Regimen Failure (TTRF)', 'timeFrame': 'Up to 5 years', 'description': 'For each disease cohort'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'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'], 'conditions': ['Glioblastoma', 'Medulloblastoma', 'Ependymoma', 'Diffuse Intrinsic Pontine Glioma']}, 'referencesModule': {'references': [{'pmid': '37715730', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '34614413', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nThe 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.\n\nThis 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.', 'detailedDescription': 'Disease-specific Cohorts :\n\nCohort 1A, 1B (closed to enrollment): relapsed or refractory glioblastoma\n\nCohort 2A, 2B: relapsed or refractory medulloblastoma\n\nCohort 3A, 3B, 3C: relapsed or refractory ependymoma\n\nCohort 4C (closed to enrollment): newly-diagnosed DIPG (must have no prior radiation or other therapy)\n\n.\n\nRadiation (or proton) plan sub-cohorts:\n\nSub-cohort A: for patients not eligible for re-irradiation\n\nSub-cohort B: for patients who are eligible for partial re-irradiation\n\nSub-cohort C: for patients who are eligible for full-dose radiation (All newly diagnosed DIPG patients and some relapsed ependymoma patients)'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '21 Years', 'minimumAge': '3 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\nDiagnosis:\n\n* 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.\n* Newly diagnosed DIPG (diffuse intrinsic pontine glioma) with no prior therapy (including no prior radiation); Biopsy is not required for DIPG.\n* Central review of tissue diagnosis is required, except non-biopsied DIPG; Archival tumor tissue must be located and available prior to study entry.\n* Patients with metastatic disease are eligible.\n\nLansky or Karnofsky performance status score must be ≥ 50%.\n\nAdequate renal function: creatinine ≤ 1.5-times upper limit of age-adjusted normal.\n\nAdequate liver function:\n\n* ALT ≤ 5-times upper limit of normal.\n* Total bilirubin ≤ 1.5-times upper limit of normal.\n\nAdequate Bone marrow function:\n\n* Absolute neutrophil count (ANC) ≥ 750/mcL.\n* Platelets ≥ 75,000/mcL (transfusion independent).\n* Hemoglobin ≥ 8 g/dL (transfusion independent).\n\nCentral nervous system: seizure disorders must be well controlled on antiepileptic medication.\n\nPrior therapy\n\n* DIPG patients must not have been treated with any prior radiation or medical therapy.\n* Patients previously treated with indoximod are excluded.\n* Patients previously treated with any other immunotherapy agent, including other IDO-targeted drugs, are eligible for enrollment.\n* Patients previously treated with chemotherapy drugs included in this protocol are eligible for enrollment.\n\nPatients must be 14 days from the administration of any investigational agent or prior cytotoxic therapy with the following exceptions:\n\n* Temozolomide dosed at or above 150 mg/m2 (allowed, but must be at least 21 days from the last dose of temozolomide).\n* 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).\n* Must be 56 days from administration of tumor-directed therapies using infectious agents (e.g., viruses, bacteria, etc).\n\nPregnant women are excluded from this study, where pregnancy is confirmed by a positive urine or serum hCG laboratory test.\n\nPatients must be able to swallow pills.\n\n.\n\nExclusion Criteria:\n\nPatients who cannot swallow indoximod pills are excluded.\n\nPatients previously treated with indoximod are excluded.\n\nPatients with DIPG who have been treated with any prior radiation or medical therapy are excluded.\n\nMidline glioma that does not include significant brain stem involvement is not considered DIPG for enrollment purposes, and is excluded.\n\nPatients with active systemic infection requiring treatment, including any HIV infection or toxoplasmosis, are excluded.\n\nPatients with active autoimmune disease that requires systemic therapy are excluded.\n\nPregnant women are excluded'}, 'identificationModule': {'nctId': 'NCT04049669', 'briefTitle': 'Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG', 'organization': {'class': 'OTHER', 'fullName': 'Augusta University'}, 'officialTitle': 'Phase 2 Trial of Indoximod With Chemotherapy and Radiation for Children With Progressive Brain Tumors or Newly Diagnosed DIPG', 'orgStudyIdInfo': {'id': 'GCC1949'}, 'secondaryIdInfos': [{'id': 'R01CA229646', 'link': 'https://reporter.nih.gov/quickSearch/R01CA229646', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Core Regimen, sub-cohort A', 'description': 'For patients not eligible for re-irradiation; Start with Core Regimen chemo-immunotherapy (indoximod with oral temozolomide).', 'interventionNames': ['Drug: Indoximod', 'Drug: Temozolomide']}, {'type': 'EXPERIMENTAL', 'label': 'Core Regimen, sub-cohort B', 'description': 'For 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).', 'interventionNames': ['Drug: Indoximod', 'Radiation: Partial Radiation', 'Drug: Temozolomide']}, {'type': 'EXPERIMENTAL', 'label': 'Core Regimen, sub-cohort C', 'description': 'For 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).', 'interventionNames': ['Drug: Indoximod', 'Radiation: Full-dose Radiation', 'Drug: Temozolomide']}, {'type': 'EXPERIMENTAL', 'label': 'Salvage Regimen 1', 'description': 'For patients who wish to continue access to indoximod after progression on the Core Regimen; Cross-over to indoximod with oral metronomic cyclophosphamide and etoposide).', 'interventionNames': ['Drug: Indoximod', 'Drug: Cyclophosphamide', 'Drug: Etoposide']}, {'type': 'EXPERIMENTAL', 'label': 'Salvage Regimen 2', 'description': 'For patients who wish to continue access to indoximod after progression on the Core Regimen; Cross-over to indoximod with oral lomustine and temozolomide).', 'interventionNames': ['Drug: Indoximod', 'Drug: Temozolomide', 'Drug: Lomustine']}], 'interventions': [{'name': 'Indoximod', 'type': 'DRUG', 'description': 'Indoximod will be taken by mouth twice daily during radiation and throughout each chemo-immunotherapy treatment cycle.', 'armGroupLabels': ['Core Regimen, sub-cohort A', 'Core Regimen, sub-cohort B', 'Core Regimen, sub-cohort C', 'Salvage Regimen 1', 'Salvage Regimen 2']}, {'name': 'Partial Radiation', 'type': 'RADIATION', 'description': 'Palliative low-dose or partial-field radiation plan (low-dose radiation or not all disease sites included).', 'armGroupLabels': ['Core Regimen, sub-cohort B']}, {'name': 'Full-dose Radiation', 'type': 'RADIATION', 'description': 'Palliative full-dose radiation plan to all known sites of disease (\\>50 Gy to brain, \\>45 Gy to spine).', 'armGroupLabels': ['Core Regimen, sub-cohort C']}, {'name': 'Temozolomide', 'type': 'DRUG', 'description': 'Temozolomide will be taken by mouth once daily, on days 1-5 of each chemo-immunotherapy treatment cycle.', 'armGroupLabels': ['Core Regimen, sub-cohort A', 'Core Regimen, sub-cohort B', 'Core Regimen, sub-cohort C', 'Salvage Regimen 2']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'description': 'Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each chemo-immunotherapy treatment cycle.', 'armGroupLabels': ['Salvage Regimen 1']}, {'name': 'Etoposide', 'type': 'DRUG', 'description': 'Etoposide will be taken by mouth once daily, on days 1-21 of each chemo-immunotherapy treatment cycle.', 'armGroupLabels': ['Salvage Regimen 1']}, {'name': 'Lomustine', 'type': 'DRUG', 'description': 'Lomustine will be taken by mouth once daily, on day 1 of each chemo-immunotherapy treatment cycle.', 'armGroupLabels': ['Salvage Regimen 2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '30912', 'city': 'Augusta', 'state': 'Georgia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Theodore S Johnson, MD, PhD', 'role': 'CONTACT', 'email': 'thjohnson@augusta.edu', 'phone': '706-721-4962'}, {'name': 'Robin Dobbins, RN', 'role': 'CONTACT', 'email': 'rdobbins@augusta.edu', 'phone': '706-721-2154'}, {'name': 'Theodore S Johnson, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Augusta University, Georgia Cancer Center', 'geoPoint': {'lat': 33.47097, 'lon': -81.97484}}, {'zip': '30322', 'city': 'Druid Hills', 'state': 'Georgia', 'status': 'ACTIVE_NOT_RECRUITING', 'country': 'United States', 'facility': "Emory University, Children's Heathcare of Atlanta", 'geoPoint': {'lat': 33.78038, 'lon': -84.33604}}, {'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'ACTIVE_NOT_RECRUITING', 'country': 'United States', 'facility': 'Dana-Farber Cancer Institute', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '45229', 'city': 'Cincinnati', 'state': 'Ohio', 'status': 'ACTIVE_NOT_RECRUITING', 'country': 'United States', 'facility': "Cincinnati Children's Hospital Medical Center", 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Kara Kachurak, CRNP', 'role': 'CONTACT', 'email': 'kgkachurak@mdanderson.org', 'phone': '713-835-4467'}, {'name': 'Gregory Friedman, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'MD Anderson Cancer Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}], 'centralContacts': [{'name': 'Theodore S Johnson, MD, PhD', 'role': 'CONTACT', 'email': 'thjohnson@augusta.edu', 'phone': '706-721-4962'}, {'name': 'Robin Dobbins, RN', 'role': 'CONTACT', 'email': 'rdobbins@augusta.edu', 'phone': '706-721-2154'}], 'overallOfficials': [{'name': 'Theodore S Johnson, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Augusta University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Theodore S. Johnson', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}, {'name': 'Augusta University', 'class': 'OTHER'}, {'name': 'Emory University', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'Theodore S. Johnson', 'investigatorAffiliation': 'Augusta University'}}}}