Treatment With ABT-199 (Venetoclax) and Purine Analogues in Relapsed/Refractory Acute Myeloid Leukemia

ABT-199 (Venetoclax) and Purine Analogues as Novel Oral Drug Combination for Treatment of Relapsed/Refractory Acute Myeloid Leukemia: the ApoAML Trial

Non-commercial, open-label interventional phase Ib study to assess the effectivity of the combination of venetoclax and 6-mercaptopurine in patients with relapsed or refractory AML.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory
• Intervention / Treatment: Drug: Venetoclax; Drug: 6-mercaptopurine

Detailed Description

Non-commercial, open-label interventional phase Ib study. The aim of the study is to assess the effectivity of the combination of venetoclax and 6-mercaptopurine in patients with relapsed or refractory AML.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sébastien Anguille, Prof. Dr.; Phone Number: 0032 3 821 3356; Email: studies.hematologie@uza.be

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • Recruiting
      • University Hospital Antwerp
      • Contact: Sébastien Anguille, Prof. Dr.
  • West Vlaanderen
    • Roeselare, West Vlaanderen, Belgium, 8800
      • Not yet recruiting
      • AZ Delta
      • Contact: Dries Deeren, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Relapsed or refractory AML
• Relapsed after or refractory to at least one cycle of intensive chemotherapy (combination of ara-c/anthracyclin) or four cycles of HMA (hypomethylating agents)
• Adult AML aged >/= 18 years
• WHO performance status: grade 0-2 at the time of enrollment
• ABT-199 (venetoclax) and PA-naïve. Patient may be prior exposed but not refractory to venetoclax. In case of previous therapy with venetoclax inclusion is only possible after discussion with the PI.

Exclusion Criteria:

• Participation in any other interventional clinical trial during the study period
• Active presence (or known history of) central nervous system disease
• History or concomitant presence of any other malignancy, except for non-melanoma skin cancer, carcinoma in situ of the cervix, any other effectively treated malignancy that has been in remission for >5 years or that is highly likely to be cured at the time of enrollment.
• Active HIV, hepatitis B or hepatitis C infection
• Use of any antitumoral agent within less than 5 times the half-life of the agent prior to the screening bone marrow examination. After the screening bone marrow examination, the use of cytoreductive treatment prior to the initiation of venetoclax is permitted in order to lower the WBC-count to <25 000/µl (e.g. hydroxyurea).
• Medical conditions requiring chronic therapy of moderate or strong CYP3A4 inducers without alternative
• Patients with known hypersensitivity to the active substance or to any of the excipients
• Pregnant or breastfeeding woman
• Active uncontrolled systemic infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venetoclax and 6-mercaptopurine; Single arm study with venetoclax and 6-mercaptopurine administered in two to six cycles of 28 days. Venetoclax is given at a dosage of 600mg with dose reduction in case of interaction with a moderate or strong CYP3A4 inhibitor. 6-mercaptopurine is given at a dosage of 100mg.	Drug: Venetoclax; Venetoclax and 6-mercaptopurine; Drug: 6-mercaptopurine; Venetoclax and 6-mercaptopurine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Objective response rate	at 2 months
Clinical response	Objective response rate	at 6 months
Clinical response	Objective response rate	at 2 years

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Investigators: Principal Investigator: Sébastien Anguille, Prof. Dr., University Hospital, Antwerp

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 16, 2022
• First Posted (Actual): August 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Venetoclax; Mercaptopurine
• Other Study ID Numbers: 2282; 2021-006473-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No