APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS)

NCT03745716 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: A18-15331
• Study Type: interventional
• Target: 154
• Locations: 2 countries
• Sites: 27

Brief Summary

A Phase III, multicenter, randomized study to compare the rate of complete response (CR) and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.

Conditions

MDS

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CR)

  To compare the complete response rate, defined as the proportion of patients who achieve complete remission (CR) with APR 246 + azacitidine treatment vs. azacitidine only.

  12 months

Study Arms (2)

Experimental arm: APR-246 + azacitidine

EXPERIMENTAL

Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65):

Drug: APR-246 + azacitidine

Control arm: Azacitidine

EXPERIMENTAL

Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65):

Drug: Azacitidine

Interventions

APR-246 + azacitidine DRUG

Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65): Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine

Experimental arm: APR-246 + azacitidine

Azacitidine DRUG

Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65): Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine

Control arm: Azacitidine

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent (ICF) and is able to comply with protocol requirements
• Documented diagnosis of MDS, according to World Health Organization (WHO) classification
• Patient has adequate organ function as defined by the following laboratory values:
• Creatinine clearance \> 30 mL/min (by Cockcroft-Gault method)
• Total serum bilirubin \< 1.5 x Upper Limit of Normal (ULN) or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome or hemolysis or who required regular blood transfusions
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x ULN
• Age ≥18 years at the time of signing the informed consent form (ICF)
• Having at least one TP53 mutation which is not benign or likely benign
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• If of childbearing potential, negative pre-treatment urine or serum pregnancy test
• If of childbearing potential (males and females), willing to use an effective form of contraception such as latex condom, hormonal birth control, intrauterine device or double barrier method during chemotherapy treatment and for at least six months thereafter

You may not qualify if:

• Patient has a known history of human immunodeficiency virus (HIV) or active hepatitis B or active hepatitis C infection (testing not mandatory)
• Patient has any of the following cardiac abnormalities (as determined by treating MD):
• Myocardial infarct within six months prior to registration,
• New York Heart Association Class II or worse heart failure (Appendix II) or known left ventricular ejection fraction (LVEF) \< the institution lower limit of normal as assessed by echocardiogram
• A history of familial long QT syndrome,
• Clinically significant pericardial disease
• Electrocardiographic evidence of acute ischemia
• Symptomatic atrial or ventricular arrhythmias not controlled by medications
• QTc ≥ 470 msec (QT cardiac interval)
• Bradycardia (\<40 bpm)
• Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g. cervix) may enroll irrespective of the time of diagnosis
• Prior exposure to azacitidine, decitabine or investigational hypomethylating agent
• Prior exposure to intensive chemotherapy
• Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS within 14 days of the first day of study drug treatment
• No concurrent use of erythroid stimulating agents

Sponsors & Collaborators

• Aprea Therapeutics: lead

Study Sites (27)

City of Hope

Duarte, California, 91010, United States

Location

Stanford University Cancer Research Center

Palo Alto, California, 94304, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Memorial Health Care System South Florida

Hollywood, Florida, 33021, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 12902, United States

Location

Robert H Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, 60611, United States

Location

University Of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

University of Iowa Hospitals and Clinics, Holden Cancer Center

Iowa City, Iowa, 52242, United States

Location

Ochsner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins Medical Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55902, United States

Location

Washington University St. Louis

St Louis, Missouri, 63130, United States

Location

Cornell Medical Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center, Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 19023, United States

Location

CHU Nantes

Nantes, 44093, France

Location

CHU Nice

Nice, 06000, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

IUCT Oncopole

Toulouse, 31100, France

Location

MeSH Terms

Interventions

eprenetapopt; Azacitidine

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

• David Sallman, MD, PhD

  Moffitt Cancer Center, Tampa, US

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This will be a Phase III, multicenter, randomized study to compare the rate of CR and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone. Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's disease. Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65): * Experimental arm: APR-246 + azacitidine; or * Control arm: Azacitidine

Study Record Dates

• First Submitted: November 14, 2018
• First Posted: November 19, 2018
• Study Start: January 11, 2019
• Primary Completion: November 27, 2020
• Study Completion: January 14, 2022
• Last Updated: March 18, 2025
• Results First Posted: July 12, 2022

Record last verified: 2025-03

Locations

FR (4); US (23)