Toxicity Genetic Determinants and Response to Azacitidine and Venetoclax in AML

A Prospective Pilot Study of the Genetic Determinants of Toxicity and Response to Azacitidine and Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia Through Evaluation of Polymorphisms in Pharmacokinetic Genes and Venetoclax Levels

The purpose of this research is to see how certain genetic variations relate to side effects and outcomes experienced while receiving treatment with azacitidine and venetoclax.

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Other: Biospecimen samples

Detailed Description

This is a prospective pilot study of the association of SNPs and venetoclax levels with toxicity and response to azacitidine plus venetoclax (Aza/Ven) as well as pharmacogenomics and venetoclax levels in patients with newly diagnosed AML determined to be unfit for intensive induction. Newly diagnosed AML patients over 18 years old who receive Aza/Ven as standard of care will be eligible for this study. Buccal swabs for SNPs and pharmacogenomic analysis can occur at any point before or after starting treatment during the study period. Venetoclax peak and trough levels will be obtained during SOC Aza/Ven treatments. Participants will be recruited initially at AHWFBCCC locations.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Courtney Schepel; Phone Number: (980) 292-0817; Email: courtney.schepel@advocatehealth.org

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
      • Principal Investigator: Brittany Ragon, MD
      • Contact: Courtney Schepel; Phone Number: (980) 292-0817; Email: courtney.schepel@advocatehealth.org
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Comprehensive Cancer Center
      • Principal Investigator: Timothy Pardee, MD
      • Contact: Timothy Pardee, MD; Phone Number: 336-716-2466; Email: tspardee@wakehealth.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants diagnosed with AML who are receiving or are planned to receive azacitidine plus venetoclax will be identified in clinic and presented informed consent for this study.

Description

Inclusion Criteria:

• Written informed consent and HIPAA authorization for release of personal health information.
• Age ≥ 18 years of age at the time of enrollment
• Confirmed diagnosis of AML
• Planned initial treatment with azacitidine and venetoclax
• Ability to read and understand the English and/or Spanish language
• As determined by the enrolling investigator, ability of the participant to understand and comply with study procedures for the entire length of the study

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

AML participants who are receiving or are planned to receive azacitidine plus venetoclax; Buccal swabs for SNPs and pharmacogenomic analysis can occur at any point before or after starting treatment during the study period. Venetoclax peak and trough levels will be obtained during SOC Aza/Ven treatments. CYP3A activity will also be evaluated. Demographic and cancer related history will be acquired for each participant. During study participation, cancer treatment details including administration, dose modifications, delays, and reductions, including specific grade 3 toxicities, stem cell transplant status, symptom burden, disease response, and survival will be collected. Participants will be taken off study after three years.

Other: Biospecimen samples; Buccal swabs and Blood samples will be collected throughout study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity side effect	Defined as a binary variable indicating whether a participant experienced a Grade 3 or higher of specific side effects (including infections, anemia, thrombocytopenia, febrile neutropenia, neutropenia, nausea, diarrhea)	From initiation of venetoclax through 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Modification	A binary variable indicating whether a participant experienced a dose modification, including delay or reduction	Approximately 6 months or until last dose of Venetoclax, whichever came first
Disease Response	For participants diagnosed with AML, response will be defined as a binary variable indicating if they had a Complete Remission (CR), Complete Remission with partial hematologic recovery (CRh), Complete Remission with incomplete hematologic recovery (CRi), Morphologic Leukemia-free state (MLFS), or partial response (PR) to induction therapy using the European LeukemiaNet (ELN 2022) criteria. Otherwise they will be considered a non-responder	Up to 3 years
Venetoclax levels	Will be defined as the maximum concentration of Venetoclax and is measured at 6 months if the participant is still receiving venetoclax	Approx 6 months
Overall survival	Duration of time from date of enrollment to death. Participants who are alive or lost to follow-up at the time of the analysis will be censored at the last known date they were alive	Approx 3 years
Dose modification due to nausea or diarrhea	A binary variable indicating whether a participant experienced a dose modification, including delay or reduction due to nausea or diarrhea	Approximately 6 months or until last dose of Venetoclax, whichever came first
Metabolizer status checklist	A categorical variable indicating whether a participant is a high, normal or low metabolizer based on pharmacogenomics analysis of SNP data	Approximately 6 months or until last dose of Venetoclax, whichever came first

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: Swim Across America; Atrium Health Levine Cancer Institute
• Investigators: Principal Investigator: Brittany Ragon, MD, Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 29, 2024
• First Posted (Actual): August 30, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute
• Other Study ID Numbers: IRB00116209; LCI-LEU-AML-VENTOX-001 (Other Identifier: Atrium Health)

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
• product manufactured in and exported from the U.S.: No