Venetoclax TDM in Newly Diagnosed AML: Exposure-Response and Prognosis (ND-AML)

Exposure-Response and Prognostic Analysis of Venetoclax Therapeutic Drug Monitoring in Newly Diagnosed AML

Venetoclax combined with azacitidine (VEN-AZA) is the current first-line standard of care for newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Although this regimen substantially improves remission rates, marked inter-individual variability is observed in clinical practice-ranging from severe myelosuppression or tumor lysis syndrome in some patients to poor response or early relapse in others. Venetoclax is primarily metabolized by CYP3A4, and its systemic exposure is modulated by multiple factors, including hepatic and renal function, concomitant medications (particularly azole antifungals), and UGT1A1 polymorphisms, leading to a 50%-70% inter-individual variability in blood drug concentrations.

*Despite this variability, the current VEN-AZA regimen employs a fixed-dose strategy (400 mg/day) without incorporating therapeutic drug monitoring (TDM) to guide individual dosing. Critical knowledge gaps remain: (1) whether a clear exposure-response relationship exists between venetoclax exposure and composite remission rate (CR+CRi); (2) what blood concentration range optimizes efficacy while minimizing toxicity; (3) which covariates significantly influence venetoclax clearance; and (4) whether early concentration sampling can reliably predict subsequent exposure and clinical outcomes.*

To address these questions, we designed a prospective study enrolling newly diagnosed AML patients receiving VEN-AZA therapy. We aim to systematically characterize the exposure-response relationship, establish an optimal therapeutic concentration window, identify key covariates contributing to inter-individual pharmacokinetic variability, and evaluate early-sampling prediction strategies. The findings are expected to provide direct evidence for TDM-guided individualized dosing and to support a paradigm shift from a "fixed-dose" to a "concentration-guided" approach in precision AML therapy.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukema

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

Contacts and Locations

• Study Contact: Name: Jia Chen; Phone Number: 86+052167976801; Email: drchenjia@163.com

Study Locations

• China
  • Suzhou, China, 21500
    • Recruiting
    • The First Affiliated Hospital of Soochow University
    • Contact: Jia Chen; Phone Number: 86+052167976801; Email: drchenjia@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

This prospective study included newly diagnosed AML patients who received the venetoclax plus azacitidine as induction. Venetoclax concentration data were collected on days 8, 15, and 22, and the steady-state trough concentration (Cmin), peak concentration (Cmax), and area under the curve (AUC) were calculated. The relationships between venetoclax exposure levels (Cmax, Cmin, and AUC) and efficacy, safety, survival, and individual patient characteristics were analyzed.

Description

Inclusion Criteria:

1. Diagnosis: Newly diagnosed acute myeloid leukemia (AML) confirmed according to the WHO 2022 or International Consensus Classification (ICC) criteria, based on bone marrow morphology, flow cytometry, and molecular genetics. Acute promyelocytic leukemia (APL) is excluded.
2. Treatment regimen: Planned or already initiated first-line therapy with venetoclax plus azacitidine (VEN-AZA), with dosing determined by the treating physician according to routine clinical practice (no protocol-mandated dose restrictions).
3. Age: ≥ 16 years.
4. Informed consent: Willingness and ability to provide written informed consent for participation in this observational study.
5. Follow-up: Agreement to attend scheduled follow-up visits and to permit clinical data collection at the time points specified in the study protocol.

Exclusion Criteria:

1. Prior AML therapy: Prior treatment for AML, with the exception of leukapheresis, hydroxyurea, low-dose cytarabine, or corticosteroids.
2. Concurrent interventional trials: Current participation in any interventional clinical trial, including those involving investigational agents.
3. Extremely short life expectancy: Judged by the investigator to be unable to complete at least one full cycle of therapy and the associated follow-up.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Venetoclax combined with Azacitidine; ND-AML patients received the venetoclax plus azacitidine as induction. Dosage is determined by clinicians based on routine practice (not mandatory in the study protocol). Venetoclax concentration data were collected on days 8, 15, and 22, and the steady-state trough concentration (Cmin), peak concentration (Cmax), and area under the curve (AUC) were calculated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate	Percentage of subjects with complete remission (CR) and incomplete hematologic recovery (CRi)	At the end of induction treatment (28 days ± 7days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematological toxicity	Number of subjects with hematological adverse events	Start of treatment to 2 weeks after end of treatment
Non-hematological toxicity	Number of subjects with non-hematological adverse events	Start of treatment to 2 weeks after end of treatment
Overall Survival	From start of induction treatment to time of death due to any cause, or until last follow-up	24 months
Event-free Survival	From start of induction treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier; or until last follow-up	24 months
Measurable residual disease response rate	Percentage of subjects with MRD negative	At the end of induction treatment (28 days ± 7days)

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 19, 2026
• First Submitted That Met QC Criteria: June 19, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: SZ3203

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