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Intermediate-size Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline Gliomas

Purpose

This is an intermediate-size expanded access protocol to provide ONC201 (dordaviprone) to patients with H3 K27M-mutant and/or midline gliomas who cannot access ONC201 (dordaviprone) through clinical trials.

Conditions

Glioma
H3 K27M

Eligibility

Eligible Ages: Over 0 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Patient meets one or more of the criteria below: Arm A - Closed to further enrollment. Arm B - Diffuse intrinsic pontine glioma (DIPG) defined as tumors with a pontine epicenter and diffuse involvement of the pons (at the discretion of the Medical Monitor, the site may be requested to provide the most recent imaging report(s) to confirm diagnosis). H3 K27M status does not have to be known or positive for this arm. Arm C - 1. Patients with primary spinal glioma that is positive for the H3 K27M mutation (performed in a laboratory with Clinical Laboratory Improvement Amendments [CLIA] or equivalent certification). Primary spinal glioma must be documented in radiology reporting. OR 2. Patients with diffuse glioma that is positive for the H3 K27M mutation (performed in a laboratory with CLIA or equivalent certification) AND radiographic evidence of leptomeningeal disease. Leptomeningeal disease must be documented in radiology reporting. Arm D - Closed to further enrollment. Arm E - Patients with H3 K27M-mutant glioma or a midline glioma of unknown H3 K27M mutational status who received ONC201 and/or ONC206 from an alternative (non-Chimerix) source prior to 31 December 2023, as evidenced by supporting documentation (e.g., medical records, pharmacy receipts, etc.). Other supporting documentation may be confirmed by the medical monitor. Detection of H3 K27M mutation should be performed in a CLIA-certified or equivalent laboratory. Arm F - Patients with H3 K27M-mutant diffuse glioma who have progressed during or after completion of frontline radiotherapy. Detection of H3 K27M mutation should be performed in a CLIA-certified or equivalent laboratory. Enrollment in this arm will be individually evaluated by the Sponsor and requires at least 3 days for review. 2. Disease status: Arm B - Patient is not required to have radiographic or clinical evidence of progressive disease. Arm C - Patient must have progressive disease as defined by Response Assessment in Neuro-Oncology (RANO) criteria or have documented recurrent glioma on diagnostic biopsy. Arm E - Not applicable. Arm F - Patient must have progressive disease as defined by RANO criteria or have documented recurrent glioma on diagnostic biopsy. 3. Prior radiotherapy: Arm B - Patient must be at least 14 days from completion of radiotherapy. Arm C - Patient must be at least 30 days from completion of frontline radiotherapy and at least 14 days from reirradiation if applicable. Arm E - Not applicable. Arm F - Patient must be at least 30 days from completion of frontline radiotherapy and at least 14 days from reirradiation if applicable. 4. (Not applicable; criterion removed in Version 5). 5. Patients must weigh at least 10 kg. 6. Washouts: Arms B, C, and F - From the projected start of scheduled study treatment, the following time periods must have elapsed from prior anti-cancer treatments: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from anti-cancer antibodies (no washout required for bevacizumab), 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies including CAR-T and other cellular therapies/immunotherapies, and 1 week from devices used to treat cancer. Arm E - No washouts are required for ONC201 and ONC206. All other anti-cancer agents need to be discontinued prior to enrollment with the exception of bevacizumab. 7. Magnetic resonance imaging (MRI) of patient's glioma obtained within 28 days prior to start of ONC201 for Arms B, C, and F. Arm E: MRI obtained within 8 weeks prior to enrollment. 8. Adequate organ and marrow function as defined below: 1. Absolute neutrophil count ≥1,000/mm3 without growth factor use ≤7 days prior to treatment (Cycle 1 Day 1 [C1D1]) 2. Hemoglobin ≥8.0 mg/dL without red blood cell transfusion ≤3 days prior to C1D1 3. Total serum bilirubin ≤1.5 X upper limit of normal (ULN) (participants with Gilbert's syndrome may be included with total bilirubin > 1.5 × ULN if direct bilirubin is ≤ 1.5 × ULN) 4. AST (SGOT)/ALT (SGPT) ≤2.5 X ULN; ≤5 X ULN if there is liver involvement secondary to tumor 5. Serum creatinine ≤1.5 X ULN (OR creatinine clearance ≥60 mL/min/1.73 m2) Arm E: Patients with organ and marrow function laboratory values outside the defined criteria must be approved by the medical monitor. 9. Female patients of childbearing potential must agree to use an effective contraception method while taking ONC201 and for at least 90 days after the last dose of ONC201 and must have a negative pregnancy test prior to starting ONC201. Male patients must be surgically sterile (i.e., >3 months post-vasectomy) or must agree to use an effective contraception method while taking ONC201 and for at least 90 days after the last dose of ONC201. Determination of effective contraception methods will be based on the judgment of the Investigator. 10. Ability to understand a written informed consent document, and the willingness to sign it. At the discretion of the Investigator, a Legally Authorized Representative (LAR) may consent on behalf of a patient who is unable to provide informed consent themselves. Assent will be obtained, as appropriate, based on the patient's age.

Exclusion Criteria

Qualifies for participation in an ongoing ONC201 or ONC206 clinical trial. 2. Arms B, C, and F: Previous or current enrollment in an ONC201 or ONC206 clinical study (including open-label and blinded studies) or expanded access protocol or previous exposure to ONC201 from any source for the treatment of CNS tumor. Arm E: Previous or current enrollment in an ONC201 clinical study (including open label and blinded studies) or expanded access protocol for the treatment of CNS tumor. 3. Current or planned participation in a study of an investigational agent (including ONC206) or using an investigational device. 4. (Not applicable; criterion removed in Version 4). 5. Any known systemic infection that, in the opinion of the Investigator, could compromise the safety of the patient while taking ONC201. 6. Prolongation of QT/QTcF interval (QTc interval >480 milliseconds) using Fridericia's QT correction formula on two electrocardiograms (ECGs) separated by at least 2 days. 7. A history of Torsades de pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome. 8. Concomitant use of medication(s) known to prolong the QT/QTc interval.

Study Design

Phase
Study Type: Expanded Access

Recruiting Locations

BMDACC at Banner University Medical Center Phoenix
Phoenix 5308655, Arizona 5551752 85006

Kaiser Permanente Los Angeles Medical Center
Los Angeles 5368361, California 5332921 90027

Children's Hospital of Orange County
Orange 5379513, California 5332921 92868

Rady Children's Hospital
San Diego 5391811, California 5332921 92123

Providence Saint John's Health Center
Santa Monica 5393212, California 5332921 90404

Children's Hospital of Colorado
Aurora 5412347, Colorado 5417618 80045

Children's National Medical Center
Washington D.C. 4140963, District of Columbia 4138106 20010

Miami Cancer Institute
Miami 4164138, Florida 4155751 33176

University Cancer & Blood Center
Athens 4180386, Georgia 4197000 30607

Kapi'olani Medical Center for Women and Children
Honolulu 5856195, Hawaii 5855797 96826

Lurie Children's Hospital
Chicago 4887398, Illinois 4896861 60661

University of Iowa Hospitals and Clinics
Iowa City 4862034, Iowa 4862182 52242

University of Michigan
Ann Arbor 4984247, Michigan 5001836 48109

Washington University in St. Louis
St Louis 4407066, Missouri 4398678 63110

University of Nebraska Medical Center - Adults Only
Omaha 5074472, Nebraska 5073708 68198

Overlook Medical Center/ Atlantic Health System
Summit 5105127, New Jersey 5101760 07901

Albany Medical Center
Albany 5106834, New York 5128638 12208

New York University Langone - Active, Enrolling
New York 5128581, New York 5128638 10016

University of Rochester
Rochester 5134086, New York 5128638 14627

Providence Neurological Specialties Clinic
Portland 5746545, Oregon 5744337 97225

University of Texas Southwestern
Dallas 4684888, Texas 4736286 75390

Huntsman Cancer Institute
Salt Lake City 5780993, Utah 5549030 84112

Children's Hospital of The King's Daughters
Norfolk 4776222, Virginia 6254928 23507

More Details

NCT ID: NCT04617002
Status: Approved for marketing
Sponsor: Jazz Pharmaceuticals