Phase I Study of APR-246 in Combination with Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies

NOT ENROLLING
Protocol # :
19-769
Conditions
Myeloid Malignancy
Phase
I
Disease Sites
Other Hematopoietic
Myeloid and Monocytic Leukemia
Principal Investigator
Winer, Eric, Stephen
Site Investigator
Fathi, Amir, T.
Site Research Nurses
Ramos, Aura
Som, Tina
Vartanian, Megan

Trial Description

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.

Eligibility Requirements

Inclusion Criteria:

1. Signed informed consent and ability to comply with protocol requirements.

2. Documented diagnosis of AML according to World Health Organization WHO) classification

3. Adequate organ function as defined by the following laboratory values:

1. Creatinine clearance > 30 mL/min

2. Total serum bilirubin < 1.5 × ULN

3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 × ULN

4. Age ≥18 years

5. At least one TP53 mutation

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

7. Projected life expectancy of ≥ 12 weeks.

8. Negative serum or urine pregnancy test

9. Females of childbearing potential and males with female partners of childbearing
potential must be willing to use an effective form of contraception

Exclusion Criteria:

1. Prior treatment for TP53-mutant AML (*dependent upon treatment arm assigned).

2. Known history of HIV or active hepatitis B or active hepatitis C infection.

3. Any of the following cardiac abnormalities:

1. Myocardial infarction within six months prior to registration;

2. New York Heart Association Class III or IV heart failure or known left
ventricular ejection fraction (LVEF) < 40%;

3. A history of familial long QT syndrome;

4. Symptomatic atrial or ventricular arrhythmias

5. QTcF ≥ 470 msec, unless due to underlying bundle branch block and/or pacemaker
and with approval of the medical monitor.

4. Concomitant malignancies for which patients are receiving active therapy

5. Known active CNS involvement from AML.

6. Malabsorption syndrome

7. Pregnancy or lactation.

8. Active uncontrolled systemic infection (viral, bacterial or fungal).

19-769