Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioma

Diffuse Intrinsic Pontine Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

xCures Study Team

Bryan Federowicz

Mark Shapiro, PhD

This study will gather data from new and existing patients with patient medical records, and patient/family/caregiver reported information to establish a clear natural history of disease suitable to serve as an external, contemporary or historical control arm for future therapeutic development programs of drugs, devices, or biologic interventions in DMG or DIPG.

xPEDITE is a completely virtual, decentralized, nationwide,real-time, real-world observational study to collect, annotate, standardize, and report the critical data elements of DMG, inclusive of DIPG, in a regulatory-compliant framework. Patients participate by eConsent to the pan-cancer master observational protocol XCELSIOR (NCT03793088). This protocol is a sub-study of XCELSIOR and does not require an additional written consent. Medical records are accessed from institutions directly via eFax or paper fax, online from patient EMR portals, direct from DNA/RNA sequencing and molecular profiling vendors, and via electronic health information exchanges. Medical records are received or converted to electronic/digitized formats (CCDA, FHIR, PDF) and sorted by medical record type (clinic visit, in-patient hospital, out-patient clinic, infusion and out-patient pharmacies, etc.) and made machine-readable to support data annotation, full text searches, and natural language processing (NLP) algorithms to further facilitate feature identification. Data elements are annotated comprehensively and longitudinally from diagnosis to final outcome and include patient level clinical features required to report endpoints in DMG and DIPG clinical trials such as anti-cancer interventions, non-cancer medications, genomics/biomarker results, radiological endpoints, steroid use, vitals, demographics, and locations of care, among others. This study does not require data entry by treating site staff or physicians. Centralized data annotation is completed by xCures remote study staff. Data elements are annotated in a central electronic data capture (EDC) system and coded to Observational Medical Outcomes Partnership (OMOP)-based ontologies (SNOMED, LOINC, ICD-O-3, CTCAE, RxNorm, MedDRA, and others) in one process, permitting standardization of verbatim terms from medical records. Data is collected in a 21 CFR Part 11-compliant EDC system with formal QC/QA process, medical review, and source data verification. Beyond EMR data, raw DICOM images (MRI, CT files) are collected from all sites of care and de-identified. Imaging will be subjected to a blinded central radiological review to assess sizes, and response or progression. For all patients, genomics results (PDFs, variant call files, and raw FASTQ files when available) are collected from commercial and academic sources and centralized. Additionally, patient- and caregiver-reported outcome questionnaires (PROs) are collected to measure the impact of disease and medical care on the patient and family and others living around them to determine the aspects of care that are most important to them. Mobility and neurological assessments will be videoed and submitted at regular intervals to prospectively document changes in clinical status by expert electronic clinician-reported outcomes (ClinROs). Together, these clinical, imaging, biomarker, and assessment data will provide a comprehensive and longitudinal documentation of DMG and DIPG disease course.

xPedite: A Study to Expedite DIPG and DMG Research

A Retrospective and Prospective Observational Sub-Study for Diffuse Midline Glioma and Diffuse Intrinsic Pontine Glioma

OS is defined as time from first dose of treatment to death due to any cause.

ORR is defined as the proportion of patients with a documented complete response (CR) or partial response (PR) as assessed by RANO or RAPNO.

CBR defined as the proportion of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) as assessed by RANO or RAPNO

xCures

Symptoms and General Pathology

Shock

All Drugs and Chemicals

Micronutrients

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Vaccines

Immunomodulating Agents

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Myeloma Proteins

Paraproteins

Iodine

Cadexomer iodine

Immunologic Factors

Anti-Infective Agents, Local

Trace Elements

rHSC-DIPGVax (8 total doses) + BALSTILIMAB (1 year of therapy or 27 cycles, whichever comes first)

Patients will enroll 6-10 weeks post standard of care (SOC) radiation completion. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. The first 3 patients must be 5 years or older to 18. Subsequently, subjects ages 12 months to 18 years can be enrolled. Up to six patients will be enrolled on Part A. Once safety is established for rHSC-DIPGVax plus anti-PD1 (BALSTILIMAB), the study will proceed to Part B.

rHSC-DIPGVax (8 total doses) + BALSTILIMAB + ZALIFRELIMAB (1 year of therapy or 9 cycles, whichever comes first)

Patients will enroll 6-10 weeks post standard of care (SOC) radiation therapy. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. The first 3 patients must be 5 years or older to 18. Subsequently, subjects ages 12 months to 18 years can be enrolled. Up to 12 patients will be enrolled on Part B. Once safety is established for rHSC-DIPGVax plus anti-PD1 (BALSTILIMAB) plus anti-CTLA4 (ZALIFRELIMAB), the study will proceed to Part C.

rHSC-DIPGVax (8 total doses) + BALSTILIMAB + ZALIFRELIMAB (at RP2D from Part B) (1 year of therapy or 9 cycles, whichever comes first)

Patients will enroll 6-10 weeks post standard of care (SOC) radiation therapy. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. Up to 12 patients will be enrolled on Part C. All subjects in Part C will be monitored for DLT's for the duration of their participation in the study to monitor for excess toxicity.

Off-the-shelf, neoantigen heat shock protein vaccine

rHSC-DIPGVax

BALSTILIMAB is a human monoclonal antibody that targets programmed cell death 1 (PD1)

Balstilimab

ZALIFRELIMAB is a human monoclonal immunoglobulin G1k subclass (IgG1k) antibody that specifically recognizes cytotoxic T lymphocyte-associated protein 4 (CTLA-4, also known as CD152)

Zalifrelimab

George Rafidi, BS

Ashley Plant-Fox, MD

Mariko Sato, MD

Claudia Mousa

Ashley S Plant, MD

Alexa E Stathis

Susan Chi, MD

This is a phase I, open label, plus expansion clinical trial evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB. rHSC-DIPGVax is an off-the-shelf neo-antigen heat shock protein containing 16 peptides reflecting neo-epitopes found in the majority of DIPG and DMG tumors. Newly diagnosed patients with DIPG and DMG who have completed radiation six to ten weeks prior to enrollment are eligible.

This is a phase I, open label, plus expansion clinical trial evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB using a 3+3 design for subjects with newly diagnosed DIPG or DMG following completion of radiation therapy. Given this is a first in-human study of rHSC-DIPGVax, an initial study "Lead In" will assess the tolerability of vaccine monotherapy first in older children (ages 5 to 18 years of age) followed by younger children (12 months to 18 years of age).

Sequential Parts A and B of this study will also first enroll patients ages 5 to 18 years of age before enrolling younger children. The rationale for the combination of vaccine and anti-PD1 therapy includes evidence of a more profound intra-tumoral response with addition of inhibition of negative co-regulatory pathways, such as, PD1/PDL1 and the need to overcome potentially immunosuppressive or immune "cold" microenvironment of gliomas. Anti-CLTA4 therapy will also be combined with rHSC-DIPGVax in the dose escalation portion of this study because of the ability of anti-CTLA4 therapy to induce T cell priming to promote T memory formation. Given the lack of standard treatment options for DIPG and DMG patients, this clinical trial will use combinatorial immunotherapy in upfront treatment of these patients in hopes of maximizing potential efficacy in this at-risk population while still assessing safety throughout.

Part A will evaluate rHSC-DIPGVax plus BALSTILIMAB. Pharmacokinetics (PK) of BALSTILIMAB will also be evaluated to assess exposure. If the rHSC-DIPGVax plus BALSTILIMAB is well tolerated in Part A for 28-days, this study will then move to enrolling Part B to evaluate the safety and tolerability of rHSC-DIPGVax and BALSTILIMAB in combination with ZALIFRELIMAB at two dose levels for a total therapy duration of one year or twenty-seven cycles, whichever occurs first.

Advancement from Part A to Part B and dose escalation in Part B will follow a conservative 3+3 design. The dose limiting toxicity (DLT) monitoring period will last 28 days (2 cycles) for Part A subjects and 42 days (1 cycle) for Part B. Subjects will be allowed to continue on in Part A for twenty-seven 14-day cycles or nine 42-day cycles in Part B or 1 year of total therapy, whichever comes first.

After the RP2D of ZALIFRELIMAB is determined, Part C, the expansion arm, will enroll further subjects at this dose level to assess futility versus efficacy. All subjects in trial Part C will be monitored for dose limiting toxicities for the duration of their participation in the study to monitor for excess toxicity.

Phase I, open label, plus expansion clinical trial

rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG

A Phase I Clinical Trial of Neo-antigen Heat Shock Protein Vaccine (rHSC-DIPGVax) in Combination With Checkpoint Blockade for the Treatment of Diffuse Intrinsic Pontine Glioma (DIPG) and Diffuse Midline Glioma in Childhood

PBMC immune subsets measured via flow cytometry from peripheral blood samples

peak plasma concentration (Cmax) of BALSTILIMAB AND ZALIFRELIMAB in the blood

Area under the plasma concentration versus time curve (AUC) of BALSTILIMAB AND ZALIFRELIMAB in the blood

Assays to assess anti drug antibody levels in the blood

Number of DLT's per CTCAE version 5.0 and iRANO guidelines.

Number of DLT's using CTCAE version 5.0 and iRANO guidelines

Overall survival from time of diagnostic imaging to time of death

time to progression (from time of diagnostic imaging to time of disease progression)

Dana-Farber Cancer Institute

Children's Hospital of Orange County

University of Calgary

Ann & Robert H Lurie Children's Hospital of Chicago

Antineoplastic Agents

TIC10 compound

Participants ≥ 52.5 kg will receive 625 mg of ONC201 (5 × 125-mg capsules) dosing days; participants \< 52.5 kg will receive a dose (and corresponding number of capsules) scaled by body weight and rounded to 125-mg increments.

ONC201

Participants ≥ 52.5 kg will receive 625 mg of ONC201 (5 × 125-mg capsules) or matching placebo on dosing days; participants \< 52.5 kg will receive a dose (and corresponding number of capsules) scaled by body weight and rounded to 125-mg increments

ONC201 + Placebo

Participants will receive placebo (same number of capsules as the ONC201 dose) on dosing days

Placebo

Tarapore, PhD

Robert Yoo, DO

Na Tosha Gatson

Lindsey Hoffmann, DO

Maciej Mrugala, MD

Xiao-Tang Kong, MD, PhD

Jessica Schulte, MD

Richard Green, MD

Phioanh Nghiemphu, MD

Mariko Sato, MD, PhD

Nicholas Butowski, MD

Akanksha Sharma, MD

Kate Therkelsen, MD

Nicholas Blondin, MD

Edina Komlodi-Pasztor, MD, PhD

Kurt Jaeckle, MD

Yazmin Odia, MD

Paul R Ferguson

Trisha Larkin, MD

Michael Vogelbaum, MD

Tobey MacDonald, MD

Kelley Hutchins, DO, MPH

Daniel Runco, MD

David Dickens, MD

Kaylyn Sinicrope, MD

Caroline Goldin, MD

Lily Pham, MD

Isabel Arrillaga-Romany, MD

Patrick Wen, MD

Carl Koschmann, MD

Elizabeth Neil, MD

Michael Ruff, MD

Andrew Cluster, MD

Chittalsinh Raulji, MD

Shama Farooq, MD

Robert Aiken

Lauren Weintraub, MD

Adilia Hormigo, MD, PhD

Aya Haggiagi

Luca Szalontay, MD

David Korones, MD

Ashley Sumrall, MD

Margaret Johnson, MD, MPH

Peter de Blank, MD

Christine Cordova, MD

Shirley Ong, MD

Maya Hrachova, DO

Prakash Ambady

Prakash Ambady, MB, MD

Stephen Bagley, MD

Nina Martinez, MD

Frank Lieberman, MD

Sage Green, DO, MD

Karen Fink, MD, PhD

Daniel Bowers, MD

Evguenia Gachimova (Adults

Wafik Zaky (Pediatrics)

Nazanin Majd (Adults)

Jay-Jiguang Zhu, MD

Andrew Brenner, MD

Rachel Kingsford

Yuri Kida

Joe Mendez, MD

Adam Cohen, MD

Melissa Mark, MD

Tresa McGranahan, MD

Ankush Bhatia, MD

David Ziegler, BS, MB, MD

Helen Wheeler, MD

Zarnie Lwin, MD

John Heath

Lawrence Cher

Santosh Valvi

Anna Bergmeister-Berghoff, MD

Johannes Gojo

Paula De Robles, MD

Rebecca Harrison, MD

George Michaiel

Seth Climans, MD

Donna Johnston, MD

Mary Lim-Fat, MD

Julie Bennett, MD

Sarah Lapointe

Søren Møller, MD

Charlotte Aaquist Haslund, MD

Rikke Dahlrot, MD

Cornelis van Tilburg, MD, PhD

Antje Wick, MD

Michael Frühwald, MD

Peter Hau, MD

Michael Ronellenfitsch, MD

Ulrich Herrlinger, MD

Martin Glas, MD

Roland Goldbrunner, MD, PhD

Andreas Jödicke, MD

Katharina Sahm, MD

Sylvia Kurz, MD

Michal Yalon, MD, PhD

Abed El Salem Abu Quider, MD

Liat Oren

Alexander Lossos, MD

Helen Toledano, MD

Shlomit Yust-Katz, MD

Deborah Blumenthal, MD

This is a randomized, double-blind, placebo-controlled, parallel-group, international, Phase 3 study in patients with newly diagnosed H3 K27M-mutant diffuse glioma to assess whether treatment with ONC201 following frontline radiotherapy will extend overall survival and progression-free survival in this population. Eligible participants will have histologically diagnosed H3 K27M-mutant diffuse glioma and have completed standard frontline radiotherapy.

ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)

ONC201 for the Treatment of Newly Diagnosed H3 K27M-mutant Diffuse Glioma Following Completion of Radiotherapy: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

Overall Survival is defined as the time from randomization to death due to any cause.

PFS is defined as time from randomization to disease progression (PD) or death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
xPedite: A Study to Expedite DIPG and DMG Research	NCT06140719	Oncology DIPG DMG		-	xCures
rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG	NCT04943848	Diffuse Intrins... Diffuse Midline...	rHSC-DIPGVax Balstilimab Zalifrelimab	12 Months - 18 Years	Ann & Robert H Lurie Children's Hospital of Chicago
ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)	NCT05580562	H3 K27M Glioma	ONC201 ONC201 + Placeb... Placebo	-	Chimerix
Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors	NCT05768880	Diffuse Intrins... Diffuse Midline... Recurrent CNS T... Recurrent, CNS ... Refractory Prim...	SC-CAR4BRAIN	1 Year - 26 Years	Seattle Children's Hospital
A Study of BXQ-350 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) or Diffuse Midline Glioma (DMG)	NCT04771897	Diffuse Intrins... Diffuse Midline...	BXQ-350 - Part ... BXQ-350 - Part ...	1 Year - 30 Years	Bexion Pharmaceuticals, Inc.
CAR T Cells to Target GD2 for DMG	NCT05544526	Diffuse Midline...	GD2 CAR T cells	- 16 Years	University College, London
Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors	NCT05768880	Diffuse Intrins... Diffuse Midline... Recurrent CNS T... Recurrent, CNS ... Refractory Prim...	SC-CAR4BRAIN	1 Year - 26 Years	Seattle Children's Hospital

Spots Global Cancer Trial Database for dmg

Every month we try and update this database with for dmg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for dmg

Every month we try and update this database with for dmg cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for dmg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.