MA+AZA Regimen for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)

A Prospective, Multicenter, Randomized Controlled Study on the MA+AZA Regimen for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)

Investigator proposed to apply the new dosage form of mitoxantrone hydrochloride liposomes to the clinical treatment of AML, while combining with cytarabine and azacitidine to form the MA+AZA treatment regimen(Mitoxantrone liposome +Ara-Cytarabine+Azacitidine), which would provide an optimal induction treatment regimen for patients with primary AML by comparing with the traditional chemotherapy regimen, DA+AZA (Daunorubicin+Ara-Cytarabine+Azacitidine).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukaemia
• Intervention / Treatment: Drug: mitoxantrone liposome, Ara-Cytarabine and azacitidine; Drug: Daunorubicin,Ara-Cytarabine, azacitidine

Detailed Description

In this study, AML patients were randomly divided into MA+AZA treatment group and DA+AZA treatment group by conducting a prospective, multicentre, exploratory, randomised controlled study. By observing the efficacy and safety of the MA+AZA combination regimen in the treatment of primary AML, and comparing the superiority of the traditional regimen, high-quality clinical evidence was obtained, providing practical evidence to support the improvement of the intervention effect and clinical prognosis of primary AML.

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Fuling Zhou, Doctor; Phone Number: 027-67813137; Email: zhoufuling@whu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Not yet recruiting
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Huanggang, Hubei, China, 438000
      • Not yet recruiting
      • The Central Hospital of Huanggang
    • Jingzhou, Hubei, China, 434020
      • Not yet recruiting
      • Jingzhou Central Hospital
    • Jingzhou, Hubei, China, 434000
      • Not yet recruiting
      • The First People's Hospital of Jingzhou
    • Shiyan, Hubei, China, 442000
      • Not yet recruiting
      • Shiyan Taihe Hospital
    • Wuhan, Hubei, China, 430071
      • Recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Zhou Fuling, director; Phone Number: +86-02767813137; Email: zhoufuling@163.com
    • Xianning, Hubei, China, 437100
      • Not yet recruiting
      • Xianning Central Hospital
    • Xiaogan, Hubei, China, 432100
      • Not yet recruiting
      • The Central Hospital of Xiaogan
    • Yichang, Hubei, China, 443003
      • Not yet recruiting
      • Yichang Central Hospital
  • Jiangsu
    • Wuxi, Jiangsu, China, 214028
      • Not yet recruiting
      • Ruijin Hospital, Shanghai Jiaotong University School Of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 030009
      • Not yet recruiting
      • Shanxi Cancer hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with primary AML with morphologically and immunologically confirmed diagnosis of bone marrow;
2. Age 18-75 years old;
3. Liver and renal function: serum total bilirubin ≤1.5 × upper limit of normal (ULN), AST/ALT <2 × ULN, serum creatinine <1.5 × ULN, 80 ml/min ≤ creatinine clearance ≤120 ml/min;
4. Cardiac function: ejection fraction EF ≥50%, ultrasensitive troponin and natriuretic peptide <1.5 × ULN;
5. Physical condition: ECOG score 0-2;
6. Obtained informed consent signed by the patient or family.

Exclusion Criteria:

1. Allergy or significant contraindication to any of the drugs involved in the protocol;
2. Patients with concomitant myelofibrosis;
3. Severe cardiac disease, including myocardial infarction and cardiac insufficiency;
4. Concomitant malignant tumours of other organs;
5. Patients with active tuberculosis and HIV-positive patients;
6. Other blood system diseases at the same time;
7. Pregnant or breastfeeding women;
8. Inability to understand or comply with the study protocol;
9. Previous intolerance or allergy to similar drugs;
10. Concurrent participation in other clinical studies;
11. Any other condition that prevents the study from proceeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mitoxantrone liposome, Ara-Cytarabine and azacitidine; Mitoxantrone hydrochloride liposome 24 mg/m2, IV every 4 weeks, day 1; Ara-Cytarabine 100 mg/m2, IV every 12 h, days 1-7; Azacitidine 100 mg, subcutaneous, once daily, days 1 to 7;	Drug: mitoxantrone liposome, Ara-Cytarabine and azacitidine; Mitoxantrone hydrochloride liposome 24 mg/m2, IV every 4 weeks, day 1; Ara-Cytarabine 100 mg/m2, IV every 12 h, days 1-7; Azacitidine 100 mg, subcutaneous, once daily, days 1 to 7
Active Comparator: Daunorubicin, Ara-Cytarabine and azacitidine; Daunorubicin 60 mg/m2, intravenously, once daily, days 1 to 3 Ara-Cytarabine 100 mg/m2, IV drip, every 12h, days 1 to 7; Azacitidine 100 mg, subcutaneous, once daily, days 1 to 7;	Drug: Daunorubicin,Ara-Cytarabine, azacitidine; Daunorubicin 60 mg/m2, intravenously, once daily, days 1 to 3; Ara-Cytarabine 100 mg/m2, IV drip, every 12h, days 1 to 7; Azacitidine 100 mg, subcutaneous, once daily, days 1 to 7;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate	Bone marrow primitive cells <5%, no primitive cells with Auer vesicles, no primitive cells in the peripheral blood, no extramedullary leukaemia, neutrophil count ≥1.0×109/L, platelet count ≥100×109/L.	Efficacy evaluation at 2-3 weeks after the first cycle (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Incidence of adverse events, e.g., GI adverse reactions, cardiotoxicity, etc.	Efficacy evaluation at 2-3 weeks after the first cycle (each cycle is 28 days)
Compound CR rate	CR+ CRi	Efficacy evaluation at 2-3 weeks after the first cycle (each cycle is 28 days)
Objective remission rate	CR+CRi+MLFS+PR	Efficacy evaluation at 2-3 weeks after the first cycle (each cycle is 28 days)
No remission rate	Patients not meeting criteria for CR, CRi, MLFS or PR	Efficacy evaluation at 2-3 weeks after the first cycle (each cycle is 28 days)
Event-free survival	From the date of the patient's first dose to the date of treatment failure,haematological relapse after CR/CRi or all-cause mortality, whichever occurs first	Assessment of up to 100 months from the date of randomisation to the date of first recorded progress or the date of death from any caus)
Disease-free survival	For patients achieving CR or CRi only, from the date of achieving remission to the date of relapse or death from any cause	From date of achieving remission to date of relapse or death from any cause (Assessment of up to 100 months from the date of randomisation to the date of first recorded progress or the date of death from any cause, whichever comes first)
Overall survival	The time from the patient's first dose of medication to the time of death from any cause.	Time from the patient's first dose of medication to death from any cause (Assessment of up to 100 months from the date of randomisation to the date of first recorded progress or the date of death from any cause, whichever comes first)
Mortality rate	Early deaths: all-cause deaths within the timeframe associated with study treatment (e.g., 30 days, 60 days after starting treatment); Cumulative deaths: deaths within the period from the date of achieving remission to the date of no prior relapse for patients achieving CR or CRi only.	30 days, 60 days after starting treatment; Assessment of up to 100 months from the date of randomisation to the date of first recorded progress or the date of death from any cause, whichever comes first

Collaborators and Investigators

• Sponsor: Zhongnan Hospital
• Collaborators: Shanxi Province Cancer Hospital; Ruijin Hospital; The First Affiliated Hospital of Zhengzhou University; The First People's Hospital of Jingzhou; Taihe Hospital; Yichang Central People's Hospital; Jingzhou Central Hospital; Xianning Central Hospital; The Central Hospital of Xiaogan
• Investigators: Study Director: Fuling Zhou, Wuhan University

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Azacytidine; Mitoxantrone liposome; Newly diagnosed AML patients; Ara-Cytarabine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; 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; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Azacitidine; Cytarabine; Daunorubicin; Mitoxantrone
• Other Study ID Numbers: 09

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