ATRA Plus Retifanlimab for Recurrent IDH-Mutant Glioma
This study is testing a combination of two drugs, All-Trans Retinoic Acid (ATRA) and Retifanlimab, for people with recurrent (returned) glioma (a type of brain tumor) that has an IDH mutation. You might be able to join if you have astrocytoma or oligodendroglioma that has come back after previous chemotherapy and/or radiation. The researchers want to see if this combination is safe and if it can shrink tumors. They will measure how many participants have their tumors shrink or disappear (objective radiographic response) over 26 months. The study plans to enroll 55 participants.
- Study design
- This is a Phase II study, meaning it's testing the effectiveness and safety of the treatment. It has a Safety Run-In, a Phase 2 portion, and a Surgical portion, with participants receiving the study drugs in 28-day cycles.
- What's involved
- You would receive ATRA orally for 14 days and Retifanlimab intravenously (through a vein) on day 1 of each 28-day cycle. This treatment continues until your disease gets worse, side effects are too severe, or for up to 2 years.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary outcome of tumor response will be measured at 26 months, suggesting follow-up for at least this duration.
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NCT05345002
All-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma
Recruiting
PHASE2Ages 18+InterventionalTreatmentStephen Bagley, MD, MSCEInvestigator-initiated
~55 participants
Updated 2026-02-20 on ClinicalTrials.gov
What's tested:RetifanlimabAll-trans retinoic acid
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Objective radiographic response (ORR)
Measured over 26 months
Conditions
Where it's being run
1 sites across 1 statesPennsylvania1
Study leadership
- Stephen Bagley, MD MSCE · PRINCIPAL_INVESTIGATOR · University of Pennsylvania
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
All Safety Run-In and Phase 2 patients: patients with any contrast-enhancing tumor must have measurable disease per RANO criteria (defined by at least 1cmx1cm of contrast-enhancing tumor). Patients with exclusively non-enhancing tumors must have least a 25% increase in bi-dimensional product of FLAIR signal abnormality (measurable disease) compared to the patient's best MRI scan (smallest bi-dimensional product of FLAIR signal abnormality) obtained following completion of the patient's most recent line of therapy
Safety Run-In: Must have failed temozolomide OR another alkylator (e.g. lomustine, procarbazine, carmustine). May have failed an unlimited number of prior systemic regimens, +/- prior radiotherapy.
Arm A: Must have failed temozolomide AND another alkylator (e.g. lomustine, procarbazine, carmustine). May have failed an unlimited number of prior systemic regimens, +/- prior radiotherapy.
Arm B: Must have failed temozolomide OR another alkylator (maximum one prior chemotherapy regimen) +/- prior radiotherapy, AND must have gone at least 12 months since last treatment (chemotherapy or radiotherapy). 4. Surgical patients (Arm C and Arm D):
Must have clinical indication for surgical resection of the suspected recurrent/progressive tumor, as determined by patient's care providers; measurable disease is not required
5-aminolevulinic acid (5-ALA) is not allowed for intraoperative tumor visualization due to the photosensitizing agent interaction with ATRA
Patient may have had an unlimited number of relapses and prior therapy regimens 5. Patients must be able to undergo MRI of the brain with gadolinium. Patients must be maintained on a stable or decreased dose of corticosteroid regimen (no increase for 5 days) prior to this baseline MRI. 6. Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
12 weeks from completion of radiation
6 weeks from a nitrosourea cytotoxic chemotherapy
3 weeks from a non-nitrosourea cytotoxic chemotherapy
4 weeks from any investigational (not Food and Drug Administration \[FDA\]-approved) agents, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter
2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g. abemaciclib, olaparib, etc) 7. If patient is on systemic corticosteroids to treat brain edema and/or brain edema-related symptoms, the dose must be 2mg of dexamethasone (or equivalent) daily or less for a minimum of 5 days prior to first dose of retifanlimab. 8. Patients must be able to swallow oral medications 9. Age 18 or older 10. Karnofsky performance status greater than or equal to 60 11. Life expectancy \>3 months 12. Adequate organ and marrow function:
Total bilirubin \<1.5 x upper limit of normal (ULN) (except patients with suspected Gilbert's Syndrome, who are eligible for the study but exempt from the total bilirubin eligibility criterion)
ALT and AST ≤ 2.5x ULN
Calculated CrCl ≥ 30 ml/min (glomerular filtration rate can also be used in place of CrCl)
Absolute Neutrophil count ≥1,500/uL
Platelets ≥ 100,000/uL
Hemoglobin ≥ 9 g/dL 13. Reproductive Status
Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) by WOCBP subject or male subject's WOCBP partner. Female partners of male subjects participating in the study may use hormone-based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug
Nonhormonal IUDs
Bilateral Tubal ligation
Vasectomy
Sexual Abstinence
It is not necessary to use any other method of contraception when complete abstinence is elected.
WOCBP participants who choose complete abstinence must continue to have pregnancy tests.
Acceptable alternate methods of highly effective contraception must be discussed in the event that the WOCBP participants chooses to forego complete abstinence. 14. Participant must, in the opinion of the Investigator, be able to comply with study procedures 15. Patients must be able to understand the study procedures and agree to participate in the study by providing written informed consent (or have legally authorized representative sign on patient's behalf if patient physically unable to sign consent due to neurologic deficit)
Exclusion
Physiologic corticosteroid replacement therapy at doses ≤ 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.
Participants with asthma that requires intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections may participate.
Participants using topical, ocular, intra-articular, or intranasal corticosteroids (with minimal systemic absorption) may participate.
Brief courses of corticosteroids for prophylaxis (eg, contrast dye allergy) or study treatment-related standard premedications are permitted.
Myocardial infarction or uncontrolled angina within 90 days prior to consent
History of clinically significant arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
History of cardiomyopathy, pericarditis, significant pericardial effusion, myocarditis, or New York Heart Association (NYHA) functional class III-IV congestive heart failure 16. Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (e.g., antihistamines and corticosteroids) 17. Known allergy or hypersensitivity to any component of retifanlimab or formulation components. 18. Known allergy or hypersensitivity to all-trans retinoic acid (tretinoin), any of its components, or other retinoids 19. Prisoners or subjects who are involuntarily incarcerated 20. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness 21. Pregnant women are excluded 22. Has received a live vaccine within 28 days before the planned start of study treatment
What this trial measures
- Objective radiographic response (ORR)26 months
Objective radiographic response (ORR), as measured by modified Response Assessment in Neuro-Oncology (RANO) criteria. ). The response is classified as Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).