Toxicity Genetic Determinants and Response to Azacitidine and Venetoclax in AML

Not yet recruiting

• Conditions: Leukemia, Myeloid, Acute
• Interventions: Other: Biospecimen samples

• Registration Number: NCT06580106
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

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.

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 will be collected at baseline. Venetoclax peak and trough levels will be obtained during SOC Aza/Ven treatments. Participants will be recruited initially at AHWFBCCC locations.

Study Timeline

• Study First Submitted: 2024-08-14
• Study First Submitted QC: 2024-08-29
• Study First Posted: 2024-08-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-06
• Last Update Posted: 2024-12-09
• Study Start: 2025-01
• Primary Completion: 2027-07
• Study Completion: 2030-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

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

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Exclusion Criteria

• None

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
AML participants who are receiving or are planned to receive azacitidine plus venetoclax	Biospecimen samples	Buccal swabs for SNPs and pharmacogenomic analysis will be collected at baseline. 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.

Primary Outcome Measures

Name	Time	Method
Toxicity side effect	From initiation of venetoclax through 30 days after last dose	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)

Secondary Outcome Measures

Name	Time	Method
Dose Modification	Approximately 6 months or until last dose of Venetoclax, whichever came first	A binary variable indicating whether a participant experienced a dose modification, including delay or reduction
Disease Response	Up to 3 years	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
Venetoclax levels	Approx 6 months	Will be defined as the maximum concentration of Venetoclax and is measured at 6 months if the participant is still receiving venetoclax
Overall survival	Approx 3 years	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
Dose modification due to nausea or diarrhea	Approximately 6 months or until last dose of Venetoclax, whichever came first	A binary variable indicating whether a participant experienced a dose modification, including delay or reduction due to nausea or diarrhea
Metabolizer status checklist	Approximately 6 months or until last dose of Venetoclax, whichever came first	A categorical variable indicating whether a participant is a high, normal or low metabolizer based on pharmacogenomics analysis of SNP data

Trial Locations

Locations (2)

Wake Forest Baptist Comprehensive Cancer Center; 🇺🇸 Winston-Salem, North Carolina, United States

Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States