Alternating Regimen of VA and Low-dose CHA in the Treatment of Unfit Newly Diagnosed AML
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFirst Affiliated Hospital of Zhejiang University
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Understand the research and sign a written informed consent form;
Be newly diagnosed with AML according to WHO 2022 criteria without prior treatment;
Age ≥ 60 years
Eastern Cooperative Oncology Group (ECOG) performance status ≥2 at screening;
Disqualifiers
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;
Trial design
Design model
Single group
Treatments tested in this trial
Alternately treated with VA/low CHA regimen
Drug1. 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.
Treatment groups
25 Participants
are divided into 1 treatment groupGroup A: VA alternating with low-CHAExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Negative 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)Secondary outcomes
1
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)2
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)3
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 months4
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 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
First Affiliated Hospital of Zhejiang University
Lead sponsor
AbbVie
Collaborator
Source ClinicalTrials.gov