Clinical trial NCT04638309: APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)
Official title: Phase 1 Study to Evaluate Safety and Efficacy of APR-548 in Combination With Azacitidine for the Treatment of TP53-Mutant Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: MDS
Myelodysplastic Syndromes
Lead sponsor: Aprea Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-11-20
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specific procedures.
2. Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.
3. Adequate organ function as defined by the following laboratory values:

   1. Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I),
   2. Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement,
   3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement.
4. Age ≥18 years at the time of signing the informed consent form.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).
6. Projected life expectancy of ≥12 weeks.
7. Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.

Exclusion Criteria:

1. Cardiac abnormalities, which includes, but not limited to:

   1. Myocardial infarction within six months prior to enrollment
   2. New York Heart Association Class III or IV heart failure or known LVEF \<40%
2. Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.
3. 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.
4. Prior exposure to eprenetapopt (APR-246).
5. A female subject who is pregnant or breast-feeding.
6. Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.
7. Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.
8. Known history or current evidence of ocular disease in either eye

Primary outcomes:
measure: To Investigate the "Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine
timeFrame: Through study completion, approximately 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institue
state: Massachusetts
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Theradex Oncology
name: Joachim Gullbo, MD
role: STUDY_DIRECTOR
References: