A Multicenter Trial Evaluating Efficacy and Safety of A Reduced Venetoclax Exposure To Seven Days Versus Standard Continuous Venetoclax Exposure Combined With Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Intensive Induction
- Sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Study ID
- NCT07082452
- Phase
- PHASE3
- Status
- Not Yet Recruiting
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Conditions
- Leukemia
- Leukemia, B-Cell, Chronic
Eligibility Criteria
- Sex
- ALL
- Age
- 70 Years - N/A
- Healthy Volunteers
- Not accepted
Interventions
- Venetoclax — DRUGVenetoclax 400 mg orally once Daily
- Azacitidine — DRUG75 mg/m2 Subcutaneous (SC) or intravenous (IV) Daily with a continuous 7-day scheme or on a 5-on/2-off \[weekend\]/2-on schedule (5-0-2) in 28-day cycle
Study Details
Combination of azacitidine (AZA) for 7 days every 28 days with a continuous daily exposure to Venetoclax (VEN), an oral bcl-2 inhibitor, is now approved for the treatment of acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy due to age (\>75 years) or comorbidities. VEN+AZA showed significant overall response rate and survival benefit but combination carries a risk of considerable toxicity (such as profound/prolonged cytopenia and infections) before but also after remission. These toxicities make it difficult to apply the recommended treatment regimen, in particular the continuous daily intake of VEN. Recent reports suggest that reducing VEN duration per cycle seems safe and feasible. We propose to investigate a reduced-intensity VEN regimen (7-day dosing/28) versus the standard continuous VEN therapy (28-day dosing/28), combined with AZA, with the primary goal of maintaining efficacy while reducing associated toxicity.
Key Dates
- Start date
- Sep 30, 2025
- Status verified
- Jul 2025
- Primary completion
- Sep 30, 2030
- Completion
- Mar 31, 2031
Study Design
- Enrollment
- 262 participants (estimated)
- Allocation
- RANDOMIZED
- Intervention model
- PARALLEL
- Primary purpose
- TREATMENT
Arms
- Experimental: Arm A: Venetoclax (7 days) + AzacitidineArm A (experimental): Patients will receive venetoclax for a total of seven days. * Azacitidine 75 m Subcutaneous (SC) or intravenous (IV) Daily with a continuous 7-day scheme or on a 5-on/2-off \[weekend\]/2-on schedule (5-0-2) in 28-day cycle * Venetoclax 400 mg orally once Daily on Days 1 - 7, in case of AZA treatment with a continuous 7-day scheme OR Venetoclax 400 milligram (mg) Daily on Days 1 - 5 and Day 8-9 in case of AZA treatment with a 5-0-2 scheme.
- Active Comparator: Arm B: Venetoclax (28 days) + AzacitidineArm B (standard): Patients will receive venetoclax for a total of 28 days (before remission), according to VIALE-A protocol. * Azacitidine 75 mg/m2 Subcutaneous (SC) or IV Daily with a continuous 7-day scheme or on a 5-on/2-off \[weekend\]/2-on schedule (5-0-2) in 28-day cycle. * Venetoclax 400 mg orally once Daily on Days 1 - 28.
Primary Outcome Measure
Proportion of subjects with complete remission or complete remission with incomplete marrow recovery (CR/CRi) [ Time Frame: at any time point during the study (at 30 days, 60 days, 3 years) ]
Central Contacts
- Christophe WILLEKENS, MD+33 (0)1 42 11 23 79
- Jean-Luc JOANNIC, PhD+33 (0)1 42 11 47 94
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