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.
This clinical study protocol investigates a novel treatment for newly diagnosed Acute Myeloid Leukemia (AML) patients ineligible to receive intensive chemotherapy (IC). Eligibility is defined as age ≥60 or age 18-59 with significant comorbidities. Key exclusions include specific AML subtypes including Acute promyelocytic leukemia (APL); FLT3-ITD mutations and active infections. The Intervention is a two-phase regimen. The Induction Phase consists of four alternating 28-day cycles of Venetoclax + Azacitidine (VA) and low-dose Cladribine + Homoharringtonine + Cytarabine (CHA). This is followed by a Maintenance Phase of 24 cycles of VA therapy. The Primary Endpoint is the rate of Minimal Residual Disease (MRD) negativity after two alternating cycles. Secondary Endpoints include composite complete remission rate, overall survival, and incidence of treatment-emergent adverse events. Clear Withdrawal Criteria are defined for situations involving unacceptable toxicity, lack of therapeutic benefit, or patient/investigator decision.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
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.
Beijing Chao-Yang Hospital, Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGShenzhen University General Hospital
Shenzhen, Guangdong, China
RECRUITINGthe First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGthe Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
RECRUITINGBone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGNegative rate of minimal residual lesions (MRD)
Proportion of patients achieving MRD-negative status (≤0.1% leukemic blasts by flow cytometry) after two cycles of alternating VA/CHA therapy
Time frame: At day28 of the second alternating (one alternating is VA plus low-CHA)
composite complete remission, CRc
Proportion achieving CR or CRi per ELN 2022 criteria at each cycle completion
Time frame: At day28 of the first alternating and the second alternating (one alternating is VA plus low-CHA)
Overall response rate, ORR
Proportion achieving PR or better (CR/CRh/CRi/MLFS/PR) per IWG criteria at each cycle completion
Time frame: At day28 of the first alternating and the second alternating (one alternating is VA plus low-CHA)
Overall Survival, OS
Time from enrollment to death from any cause, whichever came first (censored at last follow-up for survivors)
Time frame: Time from enrollment to death from any cause, whichever came first, assessed up to 24 months
disease-free survival, DFS
Time from first response to relapse or death (censored at last disease assessment)
Time frame: From the date of first response until the date of relapse or death from any cause, whichever came first, assessed up to 24 months
MRD negative DFS, DFS-MRD
Time from first MRD-negative status to MRD-positive (confirmed by a second check within 2 weeks).
Time frame: From the date of first MRD-negative status until the date of MRD-positive, relapse or death due to relapse, whichever came first, assessed up to 24months.
Event-free survival, EFS
Time from enrollment to treatment failure (not achieved PR after the first alternating, or not achieved CR after 2 alternatings, or continuous MRD positive after 4 alternatings), relapse, or death. （one alternating is VA plus low-CHA)
Time frame: from enrollment until the date of treatment failure, relapse or death from any cause, whichever came first, assessed up to 24 months
Incidence of adverse events (AEs)
Incidence of CTCAE v6.0-graded AEs from day 1 of treatment to study completion
Time frame: up to 3 years
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