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

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.

Conditions

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

Interventions

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

Sponsors & Collaborators

• Leiden University Medical Center

  collaborator OTHER

• Fred Hutchinson Cancer Center

  collaborator OTHER

• Washington University School of Medicine

  collaborator OTHER

• Shanghai Jiao Tong University School of Medicine

  lead OTHER

Principal Investigators

• Junmin Li, Professor · Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-03-15

Primary Completion

2027-10-31

Completion

2028-10-31

Countries

• China

Study Locations