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

NCT07670130 | Recruiting DMC

• 1 other identifier: SZ3203
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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, investigators designed a prospective study enrolling newly diagnosed AML patients receiving VEN-AZA therapy. Investigators 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.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Hematological toxicity

  Start of treatment to 2 weeks after end of treatment

• Non-hematological toxicity

  Start of treatment to 2 weeks after end of treatment

• Overall Survival

  24 months

• Event-free Survival

  24 months

• Measurable residual disease response rate

  At the end of induction treatment (28 days ± 7days)

Study Arms (1)

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.

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.
• 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).
• Age: ≥ 16 years.
• Informed consent: Willingness and ability to provide written informed consent for participation in this observational study.
• Follow-up: Agreement to attend scheduled follow-up visits and to permit clinical data collection at the time points specified in the study protocol.

You may not qualify if:

• Prior AML therapy: Prior treatment for AML, with the exception of leukapheresis, hydroxyurea, low-dose cytarabine, or corticosteroids.
• Concurrent interventional trials: Current participation in any interventional clinical trial, including those involving investigational agents.
• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The first Affiliated Hospital of Soochow University

Suzhou, 21500, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Jia Chen

CONTACT

86+052167976801; drchenjia@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician of Hematology. Clinical Professor. Principal Investigator

Study Record Dates

• First Submitted: June 19, 2026
• First Posted: June 26, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)