APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies

NCT04214860 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: A19-11184
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 8

Brief Summary

This clinical trial is a Phase I, open-label, dose-finding and cohort expansion study to determine the safety and preliminary efficacy of APR-246 in combination with venetoclax and azacitidine in patients with myeloid malignancies.

Conditions

Myeloid Malignancy

Outcome Measures

Primary Outcomes (2)

• To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies.

  1\. Dose-limiting toxicities (DLTs), classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0).

  From baseline until event occures, i.e. through study completion, an average of 1 year

• To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies.

  2\. Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with venetoclax and azacitidine during the trial.

  From baseline until event occures, i.e. through study completion, an average of 1 year

Study Arms (1)

APR-246

EXPERIMENTAL

APR-246 4.5 g/day

Drug: APR-246; Drug: Venetoclax; Drug: Azacitidine

Interventions

APR-246 DRUG

APR-246 4.5 g/day

APR-246

Venetoclax DRUG

Venetoclax 400 mg once daily

APR-246

Azacitidine DRUG

Subcutaneous injection, or intravenous infusion

APR-246

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 and ability to comply with protocol requirements.
• Documented diagnosis of AML according to World Health Organization WHO) classification
• Adequate organ function as defined by the following laboratory values:
• Creatinine clearance \> 30 mL/min
• Total serum bilirubin \< 1.5 × ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 × ULN
• Age ≥18 years
• At least one TP53 mutation
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Projected life expectancy of ≥ 12 weeks.
• Negative serum or urine pregnancy test
• Females of childbearing potential and males with female partners of childbearing potential must be willing to use an effective form of contraception

You may not qualify if:

• Prior treatment for TP53-mutant AML (\*dependent upon treatment arm assigned).
• Known history of HIV or active hepatitis B or active hepatitis C infection.
• Any of the following cardiac abnormalities:
• Myocardial infarction within six months prior to registration;
• New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction (LVEF) \< 40%;
• A history of familial long QT syndrome;
• Symptomatic atrial or ventricular arrhythmias
• QTcF ≥ 470 msec, unless due to underlying bundle branch block and/or pacemaker and with approval of the medical monitor.
• Concomitant malignancies for which patients are receiving active therapy
• Known active CNS involvement from AML.
• Malabsorption syndrome
• Pregnancy or lactation.
• Active uncontrolled systemic infection (viral, bacterial or fungal).

Sponsors & Collaborators

• Aprea Therapeutics: lead

Study Sites (8)

Yale Cancer Center

New Haven, Connecticut, 06511, United States

Location

H. Lee Moffitt CC

Tampa, Florida, 33612, United States

Location

Northwestern Medicine

Chicago, Illinois, 60611, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Weill Cornell Cancer Center

New York, New York, 10021, United States

Location

Memorial Sloan Kettering CC

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Garcia-Manero G, Goldberg AD, Winer ES, Altman JK, Fathi AT, Odenike O, Roboz GJ, Sweet K, Miller C, Wennborg A, Hickman DK, Kanagal-Shamanna R, Kantarjian H, Lancet J, Komrokji R, Attar EC, Sallman DA. Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study. Lancet Haematol. 2023 Apr;10(4):e272-e283. doi: 10.1016/S2352-3026(22)00403-3.

  PMID: 36990622 DERIVED

MeSH Terms

Interventions

eprenetapopt; venetoclax; 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

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will include a safety lead-in dose-finding portion followed by the expansion portion. During the safety lead-in portion of the study, two cohorts will independently enroll patients following a 3 + 3 design.

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: January 2, 2020
• Study Start: December 13, 2019
• Primary Completion: January 14, 2022
• Study Completion: January 14, 2022
• Last Updated: March 17, 2025
• Results First Posted: February 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)