Comparison of VA (Venetoclax, Azacitidine), VACl (VA, Cladribine), VACh (VA, Chidamide), and Alternating VACl/VACh in Newly Diagnosed Acute Myeloid Leukemia

NCT06532552 | Recruiting Phase 2

• 1 other identifier: SZAML06
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, multi-center, randomized, controlled Phase II study is to compare the therapeutic efficacy and side effect of VACl (Venetoclax,Azacitidine,Cladribine) alternating with VACh (Venetoclax,Azacitidine,Chidamide), VACl, VACh and VA in newly diagnosed adult acute myeloid leukemia (AML) patients ineligible for intensive therapy or declining. Cladribine is a purine analogue widely used in hematologic malignancies. The monocytic leukemia stem cell is selective sensitivity to Cladribine. Chidamide, a newly designed selective histone deacetylase inhibitor, could down regulate myeloid cell leukaemia 1 (MCL1) expression in Venetoclax resistant AML cells. Chidamide or Cladribine have synergistic anti-leukemia effects with VA through their unique mechanisms, which can eradicate leukemia stem cells and prevent the occurrence of drug resistance.

Conditions

Acute Myeloid Leukemia, Adult; Newly Diagnosed

Keywords

Venetoclax; Azacitidine; Cladribine; Chidamide

Outcome Measures

Primary Outcomes (2)

• Event-free survival (EFS)

  It is defined as the number of days from the date of randomization to the date of earliest evidence of relapse, subsequent treatment other than stem cell transplant while in composite complete remission (CR+CRi), or death. If the specified event (relapse, start of subsequent treatment, or death) does not occur, subjects will be censored at the date of last disease assessment.

  1 year

• Cumulative incidence of relapse (CIR)

  Time from CR to disease recurrence or progression

  1 year

Secondary Outcomes (4)

• Composite complete response (CRc)

  At the end of Cycle 1 (each cycle is 21-28 days)

• Overall Survival (OS)

  1 year

• Adverse reactions in hematology

  At the end of Cycle 1 (each cycle is 21-28 days)

• Nonhematological adverse reactions

  At the end of Cycle 1 (each cycle is 21-28 days)

Study Arms (4)

VA group

ACTIVE COMPARATOR

Azacitidine 75mg/m2 subcutaneous daily for 7 days and Venetoclax orally once daily (100mg d1, 200mg d2, 400mg d3-28). Patients received 2 cycles of VA, the bone marrow aspirate will be done on the 21-28th day in the each cycle. If the result is partial remission (PR)/no response (NR) at the end of the cycle 2, the patients need to withdraw from the trial. If the bone marrow assessment is complete remission (CR)/CR with incomplete hematologic recovery (CRi)/morphologic leukemia-free state (MLFS), the patients will start post-remission therapy. For post-remission therapy, if the patients ineligible for intensive chemotherapy or declines, continue with the same regimen until progression or recurrence of the disease, and the patients need to withdraw from the trial. If the patients fit for intensive chemotherapy, patients will receive chemotherapy with other regimens or transplantation, and the patients need to withdraw from the trial if progression or recurrence of the disease.

Drug: VA

VACl group

EXPERIMENTAL

Azacitidine 75mg/m2 subcutaneous Daily for 7 days, Venetoclax orally once daily (100 mg d1, 200mg d2, 400mg d3-28) and Cladribine 5mg/m2 intravenous (IV) over approximately 1 to 2 hours, daily on days 1-3. Patients received 2 cycles of VACl treatments, the bone marrow aspirate will be done on the 21-28th day in the each cycle. If the bone marrow assessment is PR/NR at the end of the cycle 2, the patients need to withdraw from the trial. If the bone marrow assessment is CR/CRi/MLFS, the patients will start post-remission therapy. For post-remission therapy, if the patients ineligible for intensive chemotherapy or declines, continue with the same regimen until progression or recurrence of the disease, and the patients need to withdraw from the trial. If the patients fit for intensive chemotherapy, patients will receive consolidation chemotherapy with other regimens or transplantation, and the patients need to withdraw from the trial if progression or recurrence of the disease.

Drug: VACl

VACh group

EXPERIMENTAL

Azacitidine 75mg/m2 subcutaneous daily for 7 days, Venetoclax orally once daily (100mg d1, 200mg d2, 400mg d3-28) and Chidamide 10mg orally daily for 12 days. Patients received 2 cycles of VACh treatments, the bone marrow aspirate will be done on the 21-28th day in the each cycle. If the bone marrow assessment is PR/NR at the end of the cycle 2, the patients need to withdraw from the trial. If the bone marrow assessment is CR/CRi/MLFS, the patients will start post-remission therapy. For post-remission therapy, if the patients ineligible for intensive chemotherapy or declines, continue with the same regimen until progression or recurrence of the disease, and the patients need to withdraw from the trial. If the patients fit for intensive chemotherapy, patients will receive consolidation chemotherapy with other regimens or transplantation, and the patients need to withdraw from the trial if progression or recurrence of the disease.

Drug: VACh

VACl Alternating With VACh group

EXPERIMENTAL

Patients received 1 cycle of VACl and 1 cycle of VACh treatment, the bone marrow aspirate will be done on the 21-28th day in the each cycle. If the bone marrow assessment is PR/NR at the end of the cycle 2, the patients need to withdraw from the trial. If the bone marrow assessment is CR/CRi/MLFS, the patients will start post-remission therapy. For post-remission therapy, if the patients ineligible for intensive chemotherapy or declines, continue with the VACl alternating with VACh until progression or recurrence of the disease, and the patients need to withdraw from the trial. If the patients fit for intensive chemotherapy, patients will receive consolidation chemotherapy with other regimens or transplantation, and the patients need to withdraw from the trial if progression or recurrence of the disease.

Drug: VACl Alternating With VACh

Interventions

VACl DRUG

Azacitidine:75mg/m2 Subcutaneous daily for 7 days Venetoclax: orally once daily (100 mg d1, 200mg d2, 400mg d3-28) Cladribine: 5mg/m2 IV over approximately 1 to 2 hours, daily on days 1-3.

Also known as: Venetoclax+Azacitidine+Cladribine

VACl group

VACh DRUG

Azacitidine: 75mg/m2 Subcutaneous daily for 7 days Venetoclax: orally once daily (100mg d1, 200mg d2, 400mg d3-28) Chidamide: 10mg orally daily for 12 days

Also known as: Venetoclax+Azacitidine+Chidamide

VACh group

VACl Alternating With VACh DRUG

VACl: Azacitidine:75mg/m2 Subcutaneous daily for 7 days Venetoclax: orally once daily (100 mg d1, 200mg d2, 400mg d3-28) Cladribine: 5mg/m2 IV over approximately 1 to 2 hours, daily on days 1-3. VACh: Azacitidine: 75mg/m2 Subcutaneous daily for 7 days Venetoclax: orally once daily (100mg d1, 200mg d2, 400mg d3-28) Chidamide: 10mg orally daily for 12 days

Also known as: Venetoclax+Azacitidine+Cladribine alternating with Venetoclax+Azacitidine+Chidamide

VACl Alternating With VACh group

VA DRUG

Azacitidine: 75mg/m2 Subcutaneous (SC) daily for 7 days Venetoclax: orally once daily (100mg d1, 200mg d2, 400mg d3-28).

Also known as: Venetoclax+Azacitidine

VA group

Eligibility Criteria

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

You may qualify if:

• A subject will be eligible for study participation if he/she meets the following criteria within 21 days prior to randomization.
• Subject must have confirmation of previously untreated AML by World Health Organization (WHO) criteria, and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities. Prior therapy with hydroxyurea or a total dose of cytarabine no more than 0.5g (for emergency use for stabilization) is allowed.
• Subject must be≥18 years of age with at least one of the following conditions:
• A)≥60 years of age; B) Patients aged \< 60 years who are unsuitable for standard induction therapy（Any other comorbidity that the physician judges to be incompatible with conventional intensive chemotherapy); C) The patient refused the conventional intensive chemotherapy.
• Adequate organ function as defined below:
• A)liver function (bilirubin≤2mg/dL, aspartate transaminase (AST) and/or alanine transaminase (ALT)≤3 x ULN).
• Unless liver enzyme abnormalities are determined by the treating MD and PI to be due to leukemic infiltration.
• B)kidney function (creatinine≤1.5xULN ).
• ECOG performance status of ≤ 2.
• A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
• Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.
• Patient must have a projected life expectancy of at least 12 weeks.

You may not qualify if:

• Subject has a history of other malignancies prior to study entry, with the exception of:
• A) Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; B) Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; C) Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
• Subject has acute promyelocytic leukemia, subject has history of myeloproliferative neoplasm \[MPN\] including myelofibrosis, essential thrombocythemia, polycythemia vera, CML with or without BCR-ABL1 translocation, BCR/ABL positive AML.
• Patient has known active central nervous syster (CNS) involvement with AML.
• Subject has a white blood cell count\> 25×10\^9/L. (Hydroxyurea is permitted to meet this criterion.)
• Prior therapy with venetoclax, Cladribine, hypomethylating agents (HMAs), Chidamide or Chimeric Antigen Receptor T cell therapy, experimental therapies for MDS or AML.
• Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
• Subject is known to be positive for human immunodeficiency virus (HIV) (HIV testing is not required.)
• Subject has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
• Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
• Subject has a cardiovascular disability status of New York Heart Association Class≥2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
• Subject has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study.
• Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
• Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV \[i.e., HBs Ag-, and anti-HBs+-\] may participate)

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead
• Jining Medical University: collaborator
• Qilu Hospital of Shandong University: collaborator
• The Affiliated Hospital of Qingdao University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• Tongji Hospital: collaborator
• The First Affiliated Hospital of Bengbu Medical University: collaborator

Study Sites (1)

The First Affliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, 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

Study Officials

• Sheng-Li Xue, M.D.

  The First Affliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sheng-Li Xue, M.D.

CONTACT

008651267781139; slxue@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: July 29, 2024
• First Posted: August 1, 2024
• Study Start: July 29, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)