NCT07172204

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: First Affiliated Hospital of Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Intensive Chemotherapy Unfit
• Newly Diagnosed Acute Myeloid Leukemia (AML)
• Age ≥60

Interventions

Type	Name	Description
DRUG	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.

Timeline

• Start date: 2025-09-16
• Primary completion: 2027-07-31
• Completion: 2029-07-31
• First posted: 2025-09-15
• Last updated: 2026-02-04

Locations

5 sites across 1 country: China