APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)
- Registration Number
- NCT04638309
- Lead Sponsor
- Aprea Therapeutics
- Brief Summary
Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes.
- Detailed Description
Open-label first-in-human (FIH) phase 1 clinical trial assessing the safety, pharmacokinetics (PK), and clinical activity of orally (p.o.) administered APR-548 alone and in combination with azacitidine for the treatment of TP53-mutant myelodysplastic syndromes (MDS).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
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Provision of signed and dated, written informed consent prior to any study specific procedures.
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Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.
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Adequate organ function as defined by the following laboratory values:
- Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I),
- Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement,
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement.
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Age ≥18 years at the time of signing the informed consent form.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).
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Projected life expectancy of ≥12 weeks.
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Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.
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Cardiac abnormalities, which includes, but not limited to:
- Myocardial infarction within six months prior to enrollment
- New York Heart Association Class III or IV heart failure or known LVEF <40%
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Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.
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Use of cytotoxic chemotherapeutic agents, or experimental agents for the treatment of MDS within 14 days or 5 half-lives of the product (whichever is shorter) of the first day of study drug treatment.
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Prior exposure to eprenetapopt (APR-246).
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A female subject who is pregnant or breast-feeding.
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Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.
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Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.
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Known history or current evidence of ocular disease in either eye
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 2 APR-548 + Azacitidine Dose level 2 Cohort 1 APR-548 + Azacitidine Dose level 1 Cohort 3 APR-548 + Azacitidine Dose level 3
- Primary Outcome Measures
Name Time Method To investigate the safety and tolerability of APR-548 as monotherapy and in combination with azacitidine. Through study completion, approximately 1 year Occurence of dose limiting toxicities (DLTs) and frequency of treatment emergent and serious adverse events.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (4)
Dana Farber Cancer Institue
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States