Clinical Trials /

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

NCT04214860

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies
  • Official Title: Phase I Study of APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: A19-11184
  • NCT ID: NCT04214860

Conditions

  • Myeloid Malignancy

Interventions

DrugSynonymsArms
APR-246APR-246
VenetoclaxAPR-246
AzacitidineAPR-246

Purpose

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.

Detailed Description

      This study will enroll adult male and female patients of age ≥ 18 years with documented
      diagnosis of AML, according to WHO classification, and documented TP53 mutation which is not
      benign or likely benign, who also meet the eligibility requirements of this protocol.

      The study will include a safety lead-in dose-finding portion followed by expansion portion.
      During the safety lead-in portion of the study, two cohorts will independently enroll
      patients following a 3 + 3 design. Each cohort will enroll up to 6 patients.

      The expansion portion will begin once the recommended phase II dose (RP2D) of APR-246 in
      combination with venetoclax and in combination with venetoclax and azacitidine have been
      determined in order to assess the antitumor activity of these combinations.
    

Trial Arms

NameTypeDescriptionInterventions
APR-246ExperimentalAPR-246 4.5 g/day
  • APR-246
  • Venetoclax
  • Azacitidine

Eligibility Criteria

        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 acute myeloid leukemia

          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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Time Frame:From baseline until event occures, i.e. through study completion, an average of 1 year
Safety Issue:
Description: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).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aprea Therapeutics AB

Last Updated

December 30, 2019