Alternating Regimen of VA and Low-dose CHA in the Treatment of Unfit Newly Diagnosed AML
The Efficacy and Safety of VA Alternating With Low-dose CHA in the Treatment of Newly Diagnosed Unfit AML: a Prospective, Multi-centers, Single Arm Phase II Study
First Affiliated Hospital of Zhejiang University
25 participants
Sep 16, 2025
INTERVENTIONAL
Conditions
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
Inclusion Criteria12
- 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 Criteria10
- 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;
Interventions
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.
Locations(5)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07172204