Clinical trial NCT06621199: Mitoxantrone Hydrochloride Liposome in Combination With Cytarabine and Venetoclax Regimen in Newly Diagnosed Elderly AML
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
Collaborators: name: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
First posted: 2024-10-01
Enrollment: 42
Sex: ALL
Minimum age (years): 60
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 2-year event-free survival (EFS) rate
timeFrame: up to 2 years
Secondary outcomes:
measure: Composite complete remission (CRc) rate of induction therapy
timeFrame: At the end of each cycle (each cycle is 28 days), up to 2 cycles
measure: Overall response rate (ORR) of induction therapy
timeFrame: At the end of each cycle (each cycle is 28 days), up to 2 cycles
measure: Relapsed-free survival (RFS)
timeFrame: up to 2 years
measure: Overall survival (OS)
timeFrame: up to 2 years
measure: Rate of CR/CRi without measurable residual disease after induction therapy
timeFrame: At the end of each cycle (each cycle is 28 days), up to 2 cycles
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: From day 1 of treatment to 28 days after the last dose
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: