A Study of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Acute Myeloid Leukemia

• Status: Not yet recruiting
• Trial end date: 2025-02-15
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center, open-label, single-arm, phase I/II study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of mitoxantrone hydrochloride liposome injection in subjects with acute myeloid leukemia (AML).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Treatments: Mitoxantrone

Criteria

Inclusion Criteria:

1. Subjects fully understand, voluntarily participate in this study and sign the informed consent form;

2. Age ≥18 years old, male or female;

3. Morphological and/or pathological confirmation of relapsed/refractory AML after prior anti-leukemic therapy or newly diagnosed unfit AML (dose expansion stage) , which are judged by the investigator to be unsuitable for intensive chemotherapy;

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for subjects with R/R AML or aged over 75 years old, 0-3 for subjects with unfit AML aged 18 to 74 years old;

5. The organ function level must meet the following requirements:

Liver function : Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times normal upper limit (ULN); Total bilirubin ≤1.5 x ULN ( ≤ 3.0 x ULN for subjects with unfit AML); Renal function: Blood creatinine ≤1.5 x ULN (creatinine clearance <45 mL/min for subjects with unfit AML); 6. Subjects and their partners agree to take effective contraception from the date of signing an informed consent to 6 months after the last dose (for example: combined hormone (contain estrogen and progesterone), combining inhibit ovulation, progestin contraception and inhibit ovulation, intrauterine device, intrauterine hormone release system, bilateral vasectomy, bilateral tubal ligation, avoiding sexual behavior, etc.); female subjects must have negative blood HCG (except menopause, hysterectomy or bilateral oophorectomy).

Exclusion Criteria:

1. AML occurs in any of the following situations:

1. Acute promyelocytic leukemia;

2. Chronic myeloid leukaemia in blast crisis;

3. Central nervous system (CNS) involvement with AML; 2. Subjects has been previously diagnosed with other malignant tumors in the past 5 years (except curable tumors such as basal cell carcinoma of the skin and carcinoma in situ of the cervix); 3. Graft-versus-host disease requiring ongoing treatment and having received more than one allogeneic stem cell transplant.

4. History of allergy to mitoxantrone hydrochloride injection or liposomal drugs; 5. Previous treatment with doxorubicin or other anthracycline and a cumulative dose of doxorubicin in excess of 400mg/m^2 (anthracycline equivalent dose calculation: 1 mg doxorubicin =2 mg epirubicin = 2 mg daunorubicin = 0.5 mg idarubicin = 0.45 mg mitoxantrone; Adriamycin liposomes excepted); 6. Received any antineoplastic therapy within 2 weeks prior to initial administration (or within 5 half-lives of the drug). Except for leukocyte lowering therapy (hydroxyurea, leukocyte separation, etc.) and prophylactic intrathecal injection which are over 24 hours prior to administration; 7.The non-hematologic toxicity of previous anti-tumor treatment > Grade 1 based on CTCAE (except for alopecia, skin pigmentation or tolerable events judged by the investigator); 8. 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);

9. Life expectancy < 3 months; 10. Cardiovascular diseases, including but not limited to:

1. QTc interval >480 ms or long QTc syndrome in screening;

2. Complete left bundle branch block, severe atrioventricular block (without pacemaker);

3. Requiring treatment of serious and uncontrolled arrhythmias, unstable angina pectoris, valvular disease, etc;

4. Have a history of chronic congestive heart failure, New York Heart Association（NYHA）≥3; or persistent cardiomyopathy;

5. Uncontrolled hypertension (defined as multiple measurements of systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg under medication control);

6. ECG evidence of myocardial infarction, viral myocarditis, history of severe pericardial disease, acute ischemic or active conduction system abnormalities within 6 months prior to screening; 11. Severe thrombosis or thromboembolism in the past 6 months, including but not limited to cerebrovascular accident (including transient ischemic attack, etc.), upper/lower vena cava thrombosis, lower extremity deep vein thrombosis, pulmonary embolism, etc; 12. HBsAg or HBcAb positive, with HBV DNA≥2000 IU/mL, or HCV 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; 13. Subjects are suffering from any other serious and/or uncontrollable disease that, in the judgment of the investigator, may affect the patient's participation in this study (including but not limited to: uncontrolled diabetes, kidney disease requiring dialysis treatment, severe liver diseases, life-threatening autoimmune disease and hemorrhagic disease, drug abuse, nervous system diseases, etc.); 14. Pregnant or lactating female; 15. Not suitable for this study as decided by the investigator due to other reasons