Mitoxantrone Hydrochloride Liposome in Combination With Cytarabine and Venetoclax Regimen in Newly Diagnosed Elderly AML

A Prospective, Single-arm, Multi-center, Phase 2 Clinical Study of Mitoxantrone Hydrochloride Liposome in Combination With Cytarabine and Venetoclax Regimen in Newly Diagnosed Elderly AML

This is a phase 2 study to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome in combination with cytarabine and venetoclax (MAV) regimen in newly diagnosed elderly AML. To account, conservatively, for a 10% dropout rate before study completion, we planned to include 42 patients. The primary endpoint is 2-year event free survival(EFS).

The optimal induction chemotherapy regimen for newly diagnosed elderly AML patients who are eligible for intense chemotherapy is currently not well defined. Mitoxantrone hydrochloride liposome (Lipo-MIT) is an innovative anthracycline nano-drug, which has been demonstrated favorable pharmacokinetic characteristics, high cardiac safety, and shown preliminary efficacy in adult AML. Thus, we designed a prospective, single-arm, phase 2 trial to explore the efficacy and safety of Lipo-MIT in combination with cytarabine and venetoclax (MAV) regimen in newly diagnosed elderly AML.

The induction therapy is a combination of Lipo-MIT (24 mg/m^2, day 1), cytarabine(100mg/m^2, day 1-5) and venetoclax (200mg day 2, 300mg day 3, 400mg day 4-10,), and would be applied for two cycles. Patients who achieve CR/CRi after using MAV induction regimen will receive the consolidation therapy according to the patients' cytogenetic-molecular risk stratification and maintenance therapy. After completion of the treatment phase, patients entered the follow-up period.

Inclusion Criteria:

1. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
2. Aged 60-70 years (including boundary values 60 and 70);
3. Newly diagnosed primary AML according to the WHO 2022 classification.
4. Physical status score of Eastern Oncology Collaboration Group (ECOG) : 0-2.
5. Life expectancy ≥ 3 months.
6. ALT/AST≤2.5 ULN (for subjects with hepatic infiltration≤5 ULN); Total bilirubin≤1.5 ULN (for subjects with hepatic infiltration≤3 ULN); Serum creatinine≤1.5 ULN.

Exclusion Criteria:

1. Subjects meet any of the following conditions:

   1. Acute promyelocytic leukemia;
   2. Secondary AML caused by chemotherapy and/or radiotherapy to treat solid tumor or antecedent hematological disorders such as MDS, MPN, MDS/MPN;
   3. AML following blast transformation of prior chronic myeloid leukemia;
   4. Central nervous system (CNS) leukemia;

2. Subjects with malignant tumors (excluding cured skin basal cell carcinoma, cervical carcinoma in situ, and other malignant tumors that have not been treated and effectively controlled within the past 5 years) within the past 5 years.

3. Subjects who have received anthracycline pretreatment or other anti-AML treatments (except for hydroxyurea, leukapheresis and other leukocyte-lowering treatments);

4. Subjects who received strong or moderate CYP3A inducers/inhibitors or P-glycoprotein (P-gp) inhibitors within 7 days before starting study treatment;

5. Subjects who are unable to take oral medications or have malabsorption syndrome;

6. Cardiac function and disease conform to one of the following conditions:

   1. Long QTc syndrome or QTc interval >480 ms;
   2. Complete left bundle branch block, degree II or III atrioventricular block;
   3. Severe, uncontrolled arrhythmia requiring medical treatment;
   4. New York Heart Association(NYHA) classification ≥ grade II;
   5. Cardiac ejection fraction (EF) was less than 50%;
   6. A history of myocardial infarction, unstable angina pectoris, severely unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically severe pericardial disease, or electrocardiogram evidence of acute ischemic or active conduction abnormalities within 6 months prior to enrollment;

7. Uncontrolled systemic diseases (such as advanced infections, uncontrolled hypertension, diabetes, etc.);

8. Human immunodeficiency virus (HIV) infection (HIV antibody positive);

9. HBsAg or HBcAb positive, with HBV-DNA≥1x10^3 copies/mL; HCV Ab positive, with HCV-RNA≥1x10^3 copies/mL;

10. A history of immediate or delayed allergy to similar drug and excipients of the investigate drug.

11. With a history of severe neurological or psychiatric illness.

12. Not suitable for this study as decided by the investigator.