Mitoxantrone Hydrochloride Liposome Combined With BU/Cy Were Used as a Conditioning Regimen for Patients With Intermediate/Adverse Risk or Persistently Positive MRD AML

Official title

Mitoxantrone Hydrochloride Liposome Injection Combined With Bu/Cy Conditioning on Acute Myeloid Leukaemia Patients With Intermediate/Adverse Risk Disease or Persistently Positive MRD Undergoing Allogeneic Haematopoietic Stem-cell Transplantation: a Prospective, Single-center, Exploratory Clinical Study

Overview

The goal of this study is to evaluate the efficacy and safety of a conditioning regimen of Mitoxantrone Hydrochloride Liposome in combination with Bu/Cy (M+Bu/Cy) on acute myeloid leukaemia (AML) patients with intermediate/adverse risk disease or persistently positive MRD undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT)

Detailed description

The goal of this study is to evaluate the efficacy and safety of a conditioning regimen of Mitoxantrone Hydrochloride Liposome in combination with Bu/Cy (M+Bu/Cy) on acute myeloid leukaemia (AML) patients with intermediate/adverse risk disease or persistently positive MRD undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT Mitoxantrone Hydrochloride Liposome combined with BU/Cy were used as a conditioning regimen for patients with intermediate/adverse risk or persistently positive MRD AML.

Mitoxantrone hydrochloride liposome (30 mg/m\^2) on day -9, iv Busulfan (3.2mg/kg/d) on day -7\~-5, iv Cyclophosphamide (60 mg/kg/d) on day -3\~-2, iv

Interventions

• Drug Mitoxantrone Hydrochloride Liposome combined with BU/Cy
  Mitoxantrone hydrochloride liposome (30 mg/m\^2) on day -9, iv Busulfan (3.2mg/kg/d) on day -7\~-5, iv Cyclophosphamide (60 mg/kg/d) on day -3\~-2, iv

Primary outcome measures

• 1 year-relapsed free survival (1y-RFS) [Time frame: 1YEAR]

Secondary outcome measures (7)

• 1 year-overall survival (1y-OS) [Time frame: 1YEAR]
• 1 year-non-relapse mortality (1y-NRM) [Time frame: 1YEAR]
• 1 year-cumulative incidence of relapse (1y-CIR) [Time frame: 1YEAR]
• Time of neutrophil and platelet engraftment [Time frame: 8 weeks]
• Complete response (CR) rate [Time frame: 1YEAR]
• Incidence of adverse events [Time frame: 14 weeks]
• Regimenrelated toxicity (RRT) [Time frame: 4 weeks]

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\. Age: 18-60 years (including 18 and 60 years) 3. Clinically diagnosed AML, excluding acute promyelocytic leukemia. Patients with at least one or more characteristics can be enrolled:

• AML patients with intermediate/adverse risk disease according to 2022 ELN recommendations.
• AML patients with persistently positive MRD before allo-HSCT. 4. Physical status score of Eastern Oncology Collaboration Group (ECOG) : 0-2. 5. Negative HIV, HBV and HCV. 6. Before the research procedure begins, an ICF must be signed by the patient himself or a close relative. Considering the patient's condition, if signing the ICF by himself is not beneficial to the treatment of the disease, then the legal guardian or a close relative of the patient sign it.

Exclusion criteria

• 1\. Relapsed/refractory AML. 2. Prior therapy with doxorubicin or other anthracyclines, and the cumulative dose of doxorubicin > 360 mg/m\^2 (1 mg doxorubicin was equivalent to 2 mg daunorubicin or 0.5 mg idarubicin).

3\. Cardiovascular diseases, including but not limited to:

• QTc interval >480 ms or long QTc syndrome in screening;
• Complete left bundle branch block, 2 or 3 grade atrioventricular block;
• Requiring treatment of serious and uncontrolled arrhythmia;
• New York Heart Association (NYHA≥2);
• Cardiac ejection fraction (EF) was less than 50%;
• Myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other history of arrhythmia or clinically serious pericardial disease that requires treatment within the first 6 months of enrollment, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities.

4\. Previous or current occurrence of other malignancies (in addition to non-melanoma basal cell carcinoma of the skin that is effectively controlled, breast/cervical carcinoma in situ, and other malignancies that have been effectively controlled without treatment within the past five years).

5\. Subjects are suffering from any other uncontrollable disease (including but not limited to: uncontrolled diabetes and hypertension, and advanced infection).

6\. HIV infection. 7. HBsAg or HBcAb positive, with HBV-DNA≥1x10\^3 copies/mL; or HCV-RNA≥1x10\^3 copies/mL; 8. Uncontrollable infection, mechanical assisted ventilation or hemodynamic instability at enrollment.

9\. Clinically significant severe liver insufficiency (defined as grade C by Child-Pugh), AST or ALT was 5 times higher than the upper limit of normal (ULN), or serum total bilirubin was 2 times higher than the ULN within 5 days prior to enrollment.

10\. End-stage renal insufficiency was diagnosed with creatinine clearance of less than 10ML/min within 5 days prior to enrollment.

11\. Moderate hepatic insufficiency and moderate renal insufficiency were simultaneously diagnosed (moderate hepatic insufficiency was defined ash grade B by Child-Pug; Moderate renal insufficiency is defined as creatinine clearance of less than 50ML/min).

12\. A history of immediate or delayed allergy to similar drug and excipients of the investigate drug.

13\. Pregnant, lactating female or subjects who refuse to use effective contraception during the study.

14\. With a history of severe neurological or psychiatric illness. 15. Not suitable for this study as decided by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06758726 · IIT2024064

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗