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

NCT04638309 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: A20-11202
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 4

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.

Conditions

MDS; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• To Investigate the "Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine

  Occurrence of frequency of treatment emergent adverse events by reviewing safety data including AEs, vital signs, laboratory data, ECG, ophthalmologic assessment findings, and other physical exam findings.

  Through study completion, approximately 28 days

Study Arms (3)

Cohort 1

EXPERIMENTAL

Dose level 1

Drug: APR-548 + Azacitidine

Cohort 2

EXPERIMENTAL

Dose level 2

Drug: APR-548 + Azacitidine

Cohort 3

EXPERIMENTAL

Dose level 3

Drug: APR-548 + Azacitidine

Interventions

APR-548 + Azacitidine DRUG

APR-548 monotherapy period followed by APR-548 in combination with Azacitidine

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.
• 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.
• Age ≥18 years at the time of signing the informed consent form.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).
• Projected life expectancy of ≥12 weeks.
• Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.

You may not qualify if:

• 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%
• Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.
• 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.
• Prior exposure to eprenetapopt (APR-246).
• A female subject who is pregnant or breast-feeding.
• Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.
• Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.
• Known history or current evidence of ocular disease in either eye

Sponsors & Collaborators

• Aprea Therapeutics: lead

Study Sites (4)

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institue

Boston, Massachusetts, 02215, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Senior Medical Advisor
• Organization: Aprea Therapeutics

info@aprea.com

215-948-4119

Study Officials

• Joachim Gullbo, MD

  Theradex Oncology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2020
• First Posted: November 20, 2020
• Study Start: September 20, 2021
• Primary Completion: April 25, 2022
• Study Completion: April 25, 2022
• Last Updated: March 10, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)