NCT07486726

Aclarubicin Plus With Azacitidine and Venetoclax in the Treatment of Acute Myeloid Leukemia

A Multicenter, Open-Label, Phase 1/2 Clinical Study of the Safety and Efficacy of Aclarubicin Combined With Azacitidine and Venetoclax in the Treatment of Acute Myeloid Leukemia

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 112 (estimated)
• Sponsor: Shanghai Jiao Tong University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Acute myeloid leukemia Acute myeloid leukemia (AML) is a clonal hematopoietic cancer that disrupts normal hematopoiesis, ultimately leading to bone marrow failure and death. The annual incidence rate of AML is 4.1 per 100000 people in the US and is higher in patients older than 65 years. There has been a steady improvement in survival over the decades, more noticeably so in younger patients and in the last decade. Azacitidine and Venetoclax is now the standard treatment of newly diagnosed AML ineligible for intensive chemotherapy, while still facing the dilemma of relapse and refractory disease. Anthracycline-based chemotherapeutics were wildly used in the treatment of fit AML patients. While the cardiovascular toxicity leading to morbidity and mortality limited the use of daunorubicin/idarubicin in unfit patients. Aclarubicin, also known as aclacinomycin A, is an anthracycline type of antibiotic with significant anti-cancer properties. Previous studies have shown that aclarubicin only induces histone eviction without causing DNA damage, and it stands out in pre-clinical models and clinical studies, as it potently kills AML cells. Meanwhile, aclarubicin lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. CAG regimen, combined with low-dose cytarabine, aclarubicin and G-CSF has been widely used in China and Japan for treatment of AML. The purpose of this study is to determine the maximum tolerated dose, safety and efficacy of aclarubicin combined with azacitidine and venetoclax for subjects with newly diagnosed and relapsed /refractory AML.

Detailed description

This will be a phase I/II, single-arm, open-label study. The study will have a phase I dose-escalation portion using a standard "3+3" approach to determine the MTD of aclarubicin in combination with established doses of azacitidine and venetoclax. Phase I is open to patients with newly diagnosed AML who's not a candidate for, or refusal of intensive induction therapy. This will be followed by two parallel phase II expansion cohorts. Cohort A will enroll patients same as in phase I and Cohort B will enroll patients with relapsed/refractory AML after intensive chemotherapy. The regimen consists of up to 6 cycles of the combination of azacitidine, venetoclax, and aclarubicin followed by maintenance azacitidine in none transplant cohort (up to 12 cycles). For patients eligible for allo-HCT, allo-HCT will be recommended, and the maintenance will be based on post-transplant schedule.

Conditions

• Acute Myeloid Leukemia (AML)
• Relapse Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia (AML)

Interventions

Type	Name	Description
DRUG	Aclarubicin	Induction (Cycle1) Phase I starting dose 20mg/m\^2 D1-D2 (dose group 1), 20mg/m2 D1-D3 (dose group 2), 20mg/m2 D1-D4 (dose group 3), ivgtt, Qd The Phase II dose was determined based on the Phase I results Consolidation (Cycle 2-6) Phase I starting dose 20mg/m\^2 D1-D2 (dose group 1), 20mg/m2 D1-D3 (dose group 2), 20mg/m2 D1-D4 (dose group 3), ivgtt, Qd The Phase II dose was determined based on the Phase I results
DRUG	Venetoclax	Cycle 1 (Induction) 100mg on day 1, 200mg on day 2, 400mg on days 3-14 Cycles 2-6 (Consolidation) 400 mg orally daily on days 1-7
DRUG	Azacitidine	Cycle 1 (Induction) 75 mg/m\^2 SC on days 1-7 of each cycle Cycles 2-6 (Consolidation) 75 mg/m\^2 SC on days 1-7 of each cycle Cycles 7-18 (Maintenance) 50 mg/m\^2 SC on days 1-5 of each cycle

Timeline

• Start date: 2026-03-15
• Primary completion: 2027-10-01
• Completion: 2028-10-01
• First posted: 2026-03-20
• Last updated: 2026-03-20

Locations

4 sites across 1 country: China