A Study to Evaluate the Tolerance and Efficacy of Mitoxantrone Hydrochloride Liposome Injection Combined With Cytarabine in Patients With Acute Myeloid Leukemia (AML)

NCT05100303 | Unknown Phase 1

• 1 other identifier: HE071-CSP-022
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multi-cohort, multi-center Phase Ib/II clinical study to evaluate the tolerance and efficacy of Mitoxantrone Hydrochloride liposome injection combined with cytarabine in patients with Acute Myeloid Leukemia (AML). The study will be divided into two phases, the dose escalation phase and the dose expansion phase. Patients with relapsed or refractory(R/R) AML will be included in the dose-escalation phase, and patients with treatment-naïve or R/R AML will be included in the dose-expansion phase.

Conditions

Treatment-naive or Relapsed or Refractory Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (2)

• Occurrence of dose-limiting toxicity (DLT)in dose escalation phase

  The first cycle (28 days)

• Adverse events during treatment in dose expansion phase

  up to 3 years

Secondary Outcomes (9)

• Adverse events during treatment in dose escalation phase

  up to 3 years

• Composite CR rate (CRc: CR+CRi) in dose escalation phase

  up to 3 years

• Objective response rate (ORR) in dose escalation phase

  up to 3 years

• Overall survival (OS) in dose escalation phase

  up to 3 years

• Explore maximum tolerated dose (MTD) in dose escalation phase

  up to 3 years

Study Arms (1)

Mitoxantrone Hydrochloride liposome and cytarabine

EXPERIMENTAL

Chemotherapy will be given in 28-day cycles, and total treatment period is 2 cycles. Dose escalation phase: Patients will receive 24 mg/m\^2, 30 mg/m\^2 or 36mg/m\^2 of mitoxantrone hydrochloride liposome daily by intravenous (IV) injections on the first day and 1.5 g/m\^2 of cytarabine twice daily by IV for 3 days (day 1, day3 and day5). Dose expansion phase: Patients with newly diagnosed AML will receive mitoxantrone hydrochloride liposome daily by IV on the first day, 100\~200 mg/m\^2 of cytarabine by IV for 7 days (day 1\~7). Patients with R/R AML will receive mitoxantrone hydrochloride liposome daily by IV on the first day, 1.5 g/m\^2 of cytarabine twice daily by IV for 3 days (day 1, day3 and day5). The dose size of mitoxantrone hydrochloride liposome will be determined by the investigator and the sponsor based on the results of the previous study.

Drug: Mitoxantrone Hydrochloride liposome injection; Drug: Cytarabine (LoDAC)

Interventions

Mitoxantrone Hydrochloride liposome injection DRUG

Mitoxantrone hydrochloride liposome will be administered by intravenous (IV) injections.

Mitoxantrone Hydrochloride liposome and cytarabine

Cytarabine (LoDAC) DRUG

Low-dose or high-dose cytarabine (LoDAC) will be administered by intravenous (IV) injections.

Mitoxantrone Hydrochloride liposome and cytarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients volunteer to participate in this study and sign the informed consent form.
• Age≥18 years old, no gender limitation.
• Patient has a diagnosis of newly diagnosed or relapsed or refractory(R/R) AML as determined by pathological and morphological results, according to World Health Organization (WHO) 2016 classification.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patient must meet the following criteria as indicated on the clinical laboratory tests:a. Serum aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x upper limit of normal (ULN);b. Serum total bilirubin ≤ 1.5 x ULN;c. Serum creatinine ≤ 1.5 x ULN.
• Patient and their partner agree to take effective contraception from the date of signing an informed consent to 180 days after the last dose; female patients must have negative urine or blood HCG (except for menopause and hysterectomy).

You may not qualify if:

• 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.
• 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).
• Patient is receiving continuous treatment for graft-versus-host disease (GVHD), or has received autologous or allogeneic stem cell transplantation more than once.
• Allergic history of mitoxantrone hydrochloride injection, cytarabine or liposome.
• Previously received doxorubicin or other anthracyclines, and the cumulative dose of doxorubicin exceeds 400 mg/m\^2 (calculation of equivalent dose of anthracyclines: 1 mg doxorubicin = 2 mg epirubicin = 2 mg daunorubicin = 0.5 mg noroxydaunorubicin = 0.45 mg mitoxantrone; except doxorubicin liposomes).
• Patient has received any anti-tumor treatment within 2 weeks before the first dose (or within 5 half-lives of the drug), including chemotherapy, immunotherapy, targeted therapy, endocrine therapy and radiation therapy (local radiation therapy interval \< 2 weeks). Leukopenia treatment (hydroxyurea, leukocyte separation, etc.) and preventive intrathecal injection exceeds 24 hours are the exception.
• The non-hematological toxicity of previous anti-tumor treatment does not return to grade≤1 (except for alopecia, skin pigmentation or tolerable events judged by the investigator).
• Patient is receiving systemic anti-infection treatment but has poor response (there are signs of infection progression within 1 week prior to the first dose or determined by the investigator).
• The estimated survival time is less than 3 months.
• 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 (except for patients who use the 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% or lower than the lower limit of the laboratory test value range of the research center;(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 screening.
• Patients have thromboembolic events in the past 6 months, such as cerebrovascular accidents (including transient ischemic attack) and pulmonary embolism.
• HBsAg/HBcAb positive with HBV-DNA ≥2000 IU/mL, 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.
• Patients who have undergone major surgery (except intravenous infusion port implantation) within 3 months before the first study dose, or plan to perform major surgery during the study period.
• Patient is suffering from any serious and /or non-controllable disease, or the investigator determines that the disease might affect the participants 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.).
• Pregnant or lactating female.

Sponsors & Collaborators

• CSPC ZhongQi Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Location

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Jishi Wang, Chief doctor

CONTACT

+86-13639089646; Wangjishi9646@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2021
• First Posted: October 29, 2021
• Study Start: December 1, 2021
• Primary Completion: November 1, 2022
• Study Completion: June 1, 2023
• Last Updated: October 29, 2021

Record last verified: 2021-10

Locations

CN (1)