Correlation of Venetoclax Plasma Concentrations With Toxicity of Hypometilating Agents and Venetoclax Combination for Acute Myeloid Leukemia Patients in Remission.

NCT ID: NCT07254312

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 14 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-10-21
• Study Completion Date: 2026-04-30

Brief Summary

Venetoclax (VEN) is a potent and selective oral inhibitor of the BCL-2 gene and has shown anti-leukemic activity when used in combination with hypomethylating agents (HMA) in patients with Acute Myeloid Leukemia (AML), both newly diagnosed and in relapse or refractory (R/R) stages. A daily dose of 400 mg has shown the best results in terms of efficacy, toxicity, and low early mortality rates (DiNardo et al., Blood 2019). The HMA-VEN combination has been approved for the treatment of newly diagnosed AML patients who are not candidates for intensive therapy. However, although this treatment is considered low-intensity, it causes a non-negligible toxicity profile, especially hematological toxicity, even in patients who have already achieved remission. As a result, treatment often needs to be interrupted, and VEN dosage adjusted in subsequent cycles.

An analysis by Pratz et al. (Pratz et al., Am J Hematol 2022) following the publication of the pivotal trial reported grade IV cytopenias lasting at least 7 days in the cycles following remission in 161 (87%) patients in the VEN+Azacitidine arm. Furthermore, plasma concentrations of VEN were analyzed in patients who developed grade IV cytopenias for at least 7 days, and no correlation was found between VEN plasma levels and the number of observed cytopenias.

In the routine management of these patients, when hematologic toxicity occurs, the approach varies greatly from center to center and is based on the individual experience and assessment of the referring clinician. As a result, there is no standardized approach. Plasma concentrations of VEN are not routinely measured during treatment.

A better understanding of the factors determining the variable toxicity observed in patients in remission could optimize treatment to improve patient tolerability and allow for the regular administration of therapy, which is essential for maintaining leukemia remission status.

Conditions

AML (Acute Myelogenous Leukemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• patients with newly diagnosed Acute Myeloid Leukemia treated with HMA-VEN in disease remission (from the first post-remission cycle).

Exclusion Criteria

• undergoing treatment with moderate or strong Cytochrome 3A4 inhibitors or inducers,
• unwilling to receive treatment as previously specified and to be tested for VEN plasma levels at the previously specified timepoint.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Patrizia Zappasodi

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fondazione IRCCS Policlinico San Matteo, SC Oncologia

Pavia, Pavia, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Patrizia Zappasodi

Role: CONTACT

p.zappasodi@smatteo.pv.it

+390382503070

Facility Contacts

Patrizia Zappasodi, MD

Role: primary

p.zappasodi@smatteo.pv.it

+390382503070

Other Identifiers

VEN-AML

Identifier Type: -

Identifier Source: org_study_id