Alternately treated with VA/low CHA regimen: 1. Induction Phase (4 alternating cycles):
Participants will receive 4 cycles of alternating therapy:
* VA Cycle:
* Venetoclax 400 mg PO daily on Days 1-28
* Azacitidine 75 mg/m² SC daily on Days 1-7
* Low-dose CHA Cycle:
* Cladribine 5 mg/m² IV daily on Days 1-3
* Homoharringtonine 1 mg/m² IV daily on Days 1-5
* Cytarabine 20 mg SC every 12 hours on Days 1-10 Alternating sequence: VA → CHA → VA → CHA → VA → CHA → VA → CHA
2. Maintenance Phase (24 months):
Following induction, participants will receive:
* Venetoclax 400 mg PO daily on Days 1-28
* Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for 24 cycles.
We aimed to compare this clinical intervention with standard VA which is:
* Venetoclax 400 mg PO daily on Days 1-28
* Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for at least 24 cycles.
Study summary
This phase II trial tests how well VA alternating with low-dose CHA works in treating unfit patients with newly diagnosed acute myeloid leukemia (AML). This is a prospective, multi-centers, single arm phase II study aimed to overcome VEN resistance and achieve greater MRD negative rate, providing better control of treatment for unfit AML.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Understand the research and sign a written informed consent form;
* Be newly diagnosed with AML according to WHO 2022 criteria without prior treatment;
* or unwilling to undergo IC. Ineligibility for IC is defined as meeting any of the following criteria:
* Age ≥ 60 years
* Age 18-59 years but ineligible for intensive chemotherapy (IC) , meet ≥1 of the following:
* Eastern Cooperative Oncology Group (ECOG) performance status ≥2 at screening;
* Severe heart failure (congestive heart failure requiring treatment or myocardial infarction history with ejection fraction ≤50%);
* Severe pulmonary dysfunction (DLCO ≤65%, FEV1 ≤65%, dyspnea at rest, or oxygen dependence);
* Severe renal insufficiency requiring dialysis;
* Child-Pugh B or C cirrhosis, or hepatic impairment with total bilirubin \>1.5×ULN;
* Mental illness requiring inpatient psychiatric treatment;
* Any comorbidity deemed by physician to contraindicate IC.
Exclusion Criteria:
* Diagnosis of: AML arising from chronic myeloid leukemia (CML); myeloid sarcoma; acute promyelocytic leukemia (APL) or presence of FLT3-ITD mutations;
* Active malignancies (except adequately treated carcinoma in situ or basal cell carcinoma) within 2 years prior to Cycle 1 Day 1 (C1D1);
* Major surgery or systemic anticancer therapy within 28 days before C1D1;
* Known hypersensitivity to: Active pharmaceutical ingredients: cladribine, homoharringtonine, cytarabine, venetoclax, azacitidine; Any excipients in study drug formulations;
* GI conditions impairing oral drug absorption: Dysphagia; short-gut syndrome; gastroparesis or related disorders;
* Uncontrolled active infection;
* Controlled infection permitted if: Afebrile (\<38°C) and hemodynamically stable (SBP \>90 mmHg, HR \<100 bpm) for ≥72 hours pre-C1D1; on non-interacting antimicrobial regimen; active HBV/HCV infection (Chronic carriers require PI approval with viral load monitoring); HIV-positive patients receiving HAART;
* Pregnancy/lactation or refusal of contraception: Negative serum β-hCG within 24h pre-C1D1;
* Psychiatric disorders or social circumstances compromising protocol compliance;
* Prior AML-directed therapy except: cytoreduction for hyperleukocytosis per institutional guidelines (hydroxyurea, leukapheresis); supportive growth factors;
Primary outcome measure(s)
Negative rate of minimal residual lesions (MRD) — At day28 of the second alternating (one alternating is VA plus low-CHA) Proportion of patients achieving MRD-negative status (≤0.1% leukemic blasts by flow cytometry) after two cycles of alternating VA/CHA therapy
Trial sites (5)
Facility
City
Region
Status
Beijing Chao-Yang Hospital, Capital Medical University
Beijing
Beijing Municipality
Recruiting
Shenzhen University General Hospital
Shenzhen
Guangdong
Recruiting
the First Affiliated Hospital of Soochow University
Suzhou
Jiangsu
Recruiting
the Second Affiliated Hospital of Nanchang University
Nanchang
Jiangxi
Recruiting
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou
Zhejiang
Recruiting
More First Affiliated Hospital of Zhejiang University trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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