Shortened Venetoclax Duration Based on Day 14 BM Blasts Versus Standard Therapy in Elderly or Frail Patients With AML Patients Treated With Azacitidine Plus Venetoclax

NCT07407660 | Not Yet Recruiting Phase 3

• 1 other identifier: 2025-h243
• Study Type: interventional
• Target: 250
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to compare the efficacy and safety of a shortened treatment course based on the bone marrow blast count on Day 14 versus standard treatment in patients with acute myeloid leukemia treated with venetoclax plus azacitidine.

Conditions

Acute Myeloid Leukemia

Keywords

Venetoclax; Azacitidine; Early assessment; Treatment optimization; Acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Achievement of CR/CRi within 2 treatment cycles

  At the end of Cycle 1 and Cycle 2 (each cycle is 28 days). If CRi, repeat 2 weeks later.

Secondary Outcomes (6)

• Achievement of CR within 2 treatment cycles

  At the end of Cycle 1 and Cycle 2 (each cycle is 28 days). If CRi, repeat 2 weeks later.

• Achievement of CR/CRi during treatment with the venetoclax plus azacitidine regimen

  At the end of Cycles 1, 2, 3, and 5 (each cycle is 28 days) of the venetoclax-azacitidine regimen, and every 2 cycles thereafter.

• Achievement of MRD negativity during treatment with the venetoclax plus azacitidine regimen

  At the end of Cycles 1, 2, 3, and 5 (each cycle is 28 days) of the venetoclax-azacitidine regimen, and every 2 cycles thereafter.

• Relapse-free survival

  From the first achievement of CR/CRi to disease relapse or death from any cause, whichever came first, assessed up to 48 months.

• Overall survival

  Time from enrollment to death from any cause, assessed up to 48 months.

Study Arms (2)

Optimized treatment

EXPERIMENTAL

Bone marrow aspiration is perfomed on day 14 of the first induction cycle. If the bone marrow blast count is \<5%, the duration of venetoclax will be shortened to 14 days; otherwise, the 28-day course will be completed. In the second cycle, patients who fail to achieve CR/CRi and those who achieve CR will receive a 28-day course of venetoclax plus azacitidine; for patients who achieve CRi, a 21-day course of venetoclax plus azacitidine will be administered within 14 days following the first cycle. Treatment for subsequent cycles will be determined according to the investigators' local clinical practice, including but not limited to continued venetoclax-azacitidine therapy, switching to intensive chemotherapy, or allogeneic hematopoietic stem cell transplantation.

Drug: Venetoclax; Drug: Azacitidine (AZA)

Standard treatment

ACTIVE COMPARATOR

No bone marrow assessment was performed on day 14 of the first induction cycle. All the patients receive the 28-day course of venetoclax plus azacitidine for the first cycle. In the second cycle, patients who fail to achieve CR/CRi and those who achieve CR will receive a 28-day course of venetoclax plus azacitidine; for patients who achieve CRi, a 21-day course of venetoclax plus azacitidine will be administered within 14 days following the first cycle. Treatment for subsequent cycles will be determined according to the investigators' local clinical practice, including but not limited to continued venetoclax-azacitidine therapy, switching to intensive chemotherapy, or allogeneic hematopoietic stem cell transplantation.

Drug: Venetoclax; Drug: Azacitidine (AZA)

Interventions

Venetoclax DRUG

Tablet

Optimized treatment; Standard treatment

Azacitidine (AZA) DRUG

Solution for subcutaneous

Optimized treatment; Standard treatment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly diagnosed acute myeloid leukemia who meet the WHO 2022 criteria.
• Meeting one of the following conditions:
• Aged ≥ 60 years;
• aged ≥ 18 years and \< 60 years, with one or more of the following comorbidities that render the subject unsuitable for intensive induction therapy:
• Complicated with congestive heart failure, or left ventricular ejection fraction ≤ 50%, or a history of chronic stable angina pectoris;
• A history of pulmonary disease, with carbon monoxide diffusing capacity of the lung (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%;
• Creatinine clearance rate \< 45 mL/min (calculated by the \*\*Cockcroft-Gault formula\*\*);
• Total bilirubin \> 1.5 × upper limit of normal;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥ 2;
• Any other comorbidities judged by the investigator to contraindicate intensive induction therapy.
• Received induction therapy with the azacitidine plus venetoclax regimen (azacitidine for injection: 75 mg/m² subcutaneously on Days 1-7; venetoclax tablets: 100 mg on Day 1, 200 mg on Day 2, and 400 mg once daily starting on Day 3) for 12-14 days. Dose adjustment of venetoclax shall be performed if combined with strong or moderate CYP3A/P-gp inhibitors.
• Completed risk stratification assessment per the ELN 2022 criteria.
• Signed the informed consent form.

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia, AML with t(8;21)(q22;q22.1)/ RUNX1::RUNX1T1 translocation, or blast crisis of chronic myeloid leukemia (CML).
• Prior treatment with venetoclax before the diagnosis of acute myeloid leukemia.
• A history of allogeneic hematopoietic stem cell transplantation.
• Severe hepatic or renal impairment, defined by the presence of any of the following abnormalities: aspartate aminotransferase (AST) \> 2.5 × ULN; alanine aminotransferase (ALT) \> 2.5 × ULN; creatinine clearance rate \< 30 mL/min (calculated by the Cockcroft-Gault formula); or total bilirubin \> 3 × ULN.
• Presence of acute active infection requiring intravenous systemic therapy.
• Presence of active malignant tumors requiring antineoplastic treatment.
• Presence of active autoimmune diseases requiring treatment with prednisone ≥ 15 mg/day or equivalent doses of other glucocorticoids, or any other immunosuppressive agents.
• Inability to swallow tablets, or presence of diseases significantly impairing gastrointestinal function (e.g., malabsorption syndrome, gastrectomy or enterectomy, bariatric surgery, symptomatic inflammatory bowel disease, or partial/complete intestinal obstruction).
• Pregnant or lactating female subjects.
• Subjects judged by the investigator to be unable to comply with the protocol due to uncontrollable medical, psychological, familial, social, or geographic conditions; or those who are unwilling or unable to follow the required procedures of the protocol.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Shanghai Qianzhanruiji Enterprise Consulting Co., Ltd.: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Qian Jiang, Dr.

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qian Jiang, Mr.

CONTACT

+86-010-88326850; jiangqian@medmail.com.cn

Zongru Li, Dr.

CONTACT

+86-010-88326852; lizongru_xiehe@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy director, Professor

Study Record Dates

• First Submitted: January 27, 2026
• First Posted: February 12, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2030
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF