Mitoxantrone Hydrochloride Liposome Combined With Chemotherapy in Untreated de Novo Acute Myeloid Leukemia

A Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Mitoxantrone Hydrochloride Liposome Injection Combined With Chemotherapy in Previously Untreated de Novo Acute Myeloid Leukemia

The purpose of this study is to determine the safety, efficacy and pharmacokinetics of mitoxantrone hydrochloride liposome injection combined with chemotherapy in previously untreated de novo acute myeloid leukemia.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Cytarabine; Drug: Mitoxantrone hydrochloride liposome injection; Drug: Homoharringtonine; Drug: Venetoclax

Detailed Description

This is a prospective, multi-center, randomized, open-label, three-arm clinical study to explore the efficacy among three chemotherapy regimens combined with mitoxantrone hydrochloride liposome in previously untreated de novo acute myeloid leukemia. Patients will be randomized to different treatment group and be given different induction therapy in the first cycle. If patients do not achieve Morphologic Leukemia-free State (MLFS) after the first induction cycle, they will receive the second induction therapy with mitoxantrone hydrochloride liposome, cytarabine and venetoclax. Mitoxantrone hydrochloride liposome will be given on day 1 at the dose of 24 mg/m2 or 30 mg/m2 and be combined with cytarabine, venetoclax or homoharringtonine. A maximum of 2 cycles of induction therapy are planned.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianxiang Wang, Doctor; Phone Number: 86-022-23909120; Email: wangjx@ihcams.an.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand the study and voluntarily sign informed consent.
2. Age: 18~65 (including 18) years old, gender unlimited.
3. Patients diagnosed with acute myeloid leukemia according to "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia" who haven't been treated.
4. Eastern Cooperative Oncology Group (ECOG) physical state score: 0-1.
5. Fit for intensive chemotherapy.

6. The function of main organs should meet the following standards before treatment:

   Kidney: Serum creatinine ≤ 1.5 × Upper limit of normal range (ULN) Liver: Total bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 3× ULN

7. Patients should agree to use contraception (such as intrauterine device [IUD], contraceptive pill or condom) during the study period and within 6 months after the end of the study; Female patients must have a negative serum pregnancy test within 7 days before enrollment.

Exclusion Criteria:

1. Any of the following cases:(1) diagnosed as acute promyelocytic leukemia (APL);(2) chronic myelogenous leukemia in blast crisis;(3) AML with central nervous system leukemia.
2. AML arising from prior cytotoxic chemotherapy or radiotherapy for other tumours.
3. Patient has been previously diagnosed with another malignancy in last 5 years (except for cured basal cell carcinoma of skin or cervical carcinoma in situ).
4. Has been previously treated with doxorubicin or other anthracyclines and drugs for AML.
5. Allergic history of mitoxantrone hydrochloride injection or any other drugs used in this study.
6. Those on systemic anti-infective therapy with poorly controlled infection (signs of infection progression within 1 week prior to the first dose, or as determined by the investigator).
7. Patient who is suffering from severe hemorrhagic diseases, such as haemophilia A, haemophilia B, von Willebrand disease and any other spontaneous bleeding require medical treatment.
8. The estimated survival time is less than 3 months.
9. Any of the following conditions occurs in cardiac function:(1) Long QTc syndrome or QTc interval > 480 ms;(2) Complete left bundle branch block or severe atrioventricular block disease (without a pacemaker);(3) Serious and uncontrolled arrhythmias and unstable angina pectoris requiring drug treatment;(4) History of chronic congestive heart failure, New York Heart Association (NYHA)≥grade 3;(5) The cardiac ejection fraction is less than 50% in Echocardiography;(6)Uncontrollable hypertension (defined as multiple measurements of systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg under drug control);(7) History of myocardial infarction, unstable angina pectoris, viral myocarditis or severe pericardial disease, ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before first dose.
10. Patients have thromboembolic events within 6 months prior to first dose, such as cerebrovascular accidents (including transient ischemic attack) and pulmonary embolism.
11. HBsAg/HBcAb positive with HBV-DNA higher than the lower limit of the detection value of the research center , hepatitis C antibody-positive with HCV-RNA higher than the lower limit of the detection value of the research center, or HIV antibody positive in the preliminary screening.
12. Patients who have been treated with strong/moderate CYP3A inducers/inhibitors or P-gp inhibitors within 7 days prior to first dose (for treatment group 3 only).
13. Patients who cannot take oral medications or have absorption disorder (for treatment group 3 only).
14. Patient is suffering from any serious and /or non-controllable disease, or the investigator determines that the disease might affect the participation of patients in the study, including (but not limited to, uncontrolled diabetes, dialysis related kidney diseases, severe liver diseases, life-threatening autoimmune diseases and hemorrhagic diseases, drug abuse, neurological diseases, etc.).
15. Pregnant or lactating female.
16. Patients who are not suitable for this study as decided by the investigator due to other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group 1; Patients will receive mitoxantrone hydrochloride liposome injection combined with standard-dose of cytarabine.	Drug: Cytarabine; Intravenous infusion; Drug: Mitoxantrone hydrochloride liposome injection; Intravenous infusion on day 1 in a 4-week treatment cycle.
Experimental: Treatment group 2; Patients will receive mitoxantrone hydrochloride liposome injection combined with intermediate-dose of cytarabine and homoharringtonine.	Drug: Cytarabine; Intravenous infusion; Drug: Mitoxantrone hydrochloride liposome injection; Intravenous infusion on day 1 in a 4-week treatment cycle.; Drug: Homoharringtonine; Intravenous infusion
Experimental: Treatment group 3; Patients will receive mitoxantrone hydrochloride liposome injection combined with standard-dose of cytarabine and venetoclax.	Drug: Cytarabine; Intravenous infusion; Drug: Mitoxantrone hydrochloride liposome injection; Intravenous infusion on day 1 in a 4-week treatment cycle.; Drug: Venetoclax; Orally once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Up to approximately one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate（CR）	Proportion of patients with complete remission	Up to approximately nine weeks
Complete remission or complete remission with partial hematologic recovery (CR/CRh)	Proportion of patients with complete remission or complete remission with partial hematologic recovery.	Up to approximately nine weeks
Composite remission rate (CRc)	Proportion of subjects with complete remission (CR) or complete remission with partial hematologic recovery (CRh) or complete remission with incomplete hematologic recovery (Cri).	Up to approximately nine weeks
Minimal Residual Disease (MRD)-negative composite remission rates	Among those who have achieved composite remission, proportion of patients who is MRD-negative.	Up to approximately nine weeks
Event-free survival (EFS)	It is defined as the time from the start of randomization to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first).	Up to approximately 3 years.
Relapse-free Survival (RFS)	It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up.	Up to approximately 3 years.
Overall survival (OS)	It is defined as the time from the start of randomization to the death from any cause.	Up to approximately 3 years.
Blood concentrations of total and free mitoxantrone.		30 minutes before administration and 5min, 6, 24, 72, 144, 288, 432, 648 hours after administration of Mitoxantrone hydrochloride liposome on day 1

Collaborators and Investigators

• Sponsor: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
• Investigators: Principal Investigator: Jianxiang Wang, Doctor, Chinese Academy of Medical Sciences & Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 29, 2023
• First Submitted That Met QC Criteria: May 29, 2023
• First Posted (Actual): June 7, 2023

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: May 29, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Synthesis Inhibitors; Venetoclax; Cytarabine; Mitoxantrone; Homoharringtonine
• Other Study ID Numbers: HE071-032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No