APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04638309
• Other study ID #: A20-11202
• Status: Terminated
• Phase: Phase 1
• Start date: September 20, 2021
• Est. completion date: April 25, 2022

Study information

• Verified date: July 2022
• Source: Aprea Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes.

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 information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: April 25, 2022
• Est. primary completion date: April 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• MDS
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• APR-548 + Azacitidine
APR-548 monotherapy period followed by APR-548 in combination with Azacitidine

Locations

Country	Name	City	State
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
Aprea Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To investigate the safety and tolerability of APR-548 as monotherapy and in combination with azacitidine.	Occurence of dose limiting toxicities (DLTs) and frequency of treatment emergent and serious adverse events.	Through study completion, approximately 1 year