A Phase 2 interventional study of VACl and VACh in Acute Myeloid Leukemia, Adult and Newly Diagnosed, sponsored by The First Affiliated Hospital of Soochow University. Recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-19.
Sponsored by The First Affiliated Hospital of Soochow University · Phase 2, Interventional, and Treatment
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.
AML is a clonal myelopoietic stem cell disorder characterized by the accumulation of neoplastic cells in the bone marrow and in the peripheral circulation. The median age of AML patients is 68 years. Although intensive chemotherapy and allogeneic stem cell transplant (allo-HSCT) are standard approaches for newly diagnosed patients, they are associated with higher rates of treatment related complications and inferior outcomes in older patients. Venetoclax, a newly orally available and selective B cell lymphoma-2 (BCL2) inhibitor, Venetoclax in combination with hypomethylation agents or cytarabine has been approved by the Food and Drug Administration (FDA) for the treatment of patients with newly diagnosed AML unfit for intensive chemotherapy. However, the emergence of resistance to Venetoclax based combinations has become an important clinical dilemma. Resistance to Venetoclax can be acquired through the up regulation of anti-apoptotic proteins, such as myeloid cell leukaemia 1 (MCL1). Chidamide, a newly designed selective histone deacetylase inhibitor, Chidamide could down Bregulate MCL1 expression in Venetoclax resistant AML cells. Our experience showed that the Chidamide+VA could improve the condition of R/R AML patients who are resistant to VA. Cladribine is a purine analogue widely used in hematologic malignancies. It was demonstrated that addition of Cladribine to the VA regimen increases eradication of primary AML containing monocytic leukemia stem cell activity in both in vitro and in vivo preclinical models. 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, thereby increasing response rate, prolonging patient survival, reducing recurrence, and improving prognosis without increasing treatment-related complications. Therefore, 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 AML patients ineligible for intensive therapy or declining.
2,971 studies on the registry are indexed under Leukemia, Myeloid, Acute; 745 are open to participants now.
This study's planned enrollment of 172 is above the median of 41 across 2,509 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →The First Affiliated Hospital of Soochow University is the lead sponsor of 252 studies on the registry; 148 are open to participants now.
Counted across the registry records on this site, refreshed daily.
A subject will be eligible for study participation if he/she meets the following criteria within 21 days prior to randomization.
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 ).
Exclusion Criteria:
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.
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
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
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
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
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
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
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
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
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.
Time frame: 1 year
Cumulative incidence of relapse (CIR)
Time from CR to disease recurrence or progression
Time frame: 1 year
Composite complete response (CRc)
CRc rate was defifined as patients achieving a CR or CRi
Time frame: At the end of Cycle 1 (each cycle is 21-28 days)
Overall Survival (OS)
Time from date of treatment start until date of death due to any cause
Time frame: 1 year
Adverse reactions in hematology
Record of adverse events in hematological system during and after VA,VACl,VACh,VACl alternating with VACh regimen induction (agranulocytosis days, platelet（PLT）/red blood cell (RBC) transfusion units)
Time frame: At the end of Cycle 1 (each cycle is 21-28 days)
Nonhematological adverse reactions
Record of adverse events in other organs or systmes during and after VA,VACl,VACh,VACl alternating with VACh regimen induction (infection and organ injury)
Time frame: At the end of Cycle 1 (each cycle is 21-28 days)
Plan to share: No
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The First Affiliated Hospital of Soochow University