Evaluating a new treatment for recurrent adult acute myeloid leukemia and myelodysplastic syndrome

A Prospective, Multicenter, and Exploratory Study of Mitoxantrone Liposomes, Cytarabine and G-CSF Combined With Vineclavone in the Treatment ofRecurrent Adult AML and MDS-EB-2/Elder AML

This study is testing a new combination treatment for adults with recurrent acute myeloid leukemia and myelodysplastic syndrome to see if it works better than current options.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: chemotherapy, doxorubicin
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06329999 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the efficacy and safety of a combination treatment involving mitoxantrone hydrochloride liposomes, cytarabine, G-CSF, and venetoclax in adults with recurrent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS-EB-2). The study will include patients aged 18-75 who have been diagnosed with these conditions and will evaluate their response to the treatment regimen. The trial is designed to gather data on how well this combination works compared to existing therapies, particularly in patients who have not responded to previous treatments.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-75 with recurrent AML or MDS-EB-2 who meet specific clinical criteria.

Not a fit: Patients with significant comorbidities or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with recurrent AML and MDS, potentially improving survival rates and quality of life.

How similar studies have performed: Previous studies have shown promising results with similar treatment regimens, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* The patient fully understands this study, voluntarily participates and signs an informed consent form (ICF);
* Age: 18-75 years old (including boundary values of 18 and 75);
* Clinically confirmed adult AML and MDS-IB2 (WHO 2022 standard) patients, AML patients meet any of the following criteria:

  1. Treatment related AML
  2. Previously had a history of MDS
  3. Associated with MDS related genes/chromosomal abnormalities
  4. Previously had a history of CMML
  5. Age ≥ 60 years old
  6. Previous history of prodromal MPN, including ET, PV, and MF, with bone marrow fibrosis ≤ grade 2 (according to the 0-3 grade standard)；
* For elderly AML or MDS patients, the comprehensive evaluation should be based on the Fit population: ECOG\<3, no major comorbidities, and MMSE and SPPB meet the standards (refer to Appendix 8-11);
* Expected survival time ≥ 3 months;
* Liver and kidney function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal value (ULN) (≤ 5 times the upper limit of normal value for patients with liver infiltration); Total bilirubin ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver infiltration); Serum creatinine ≤ 1.5 times the upper limit of normal value;
* The relevant treatment for MDS (excluding blood transfusion) must be completed 2 weeks before the start of the study treatment; In the case of rapidly proliferative diseases, hydroxyurea is allowed to be used until 24 hours before the start of the study treatment. Before starting the research treatment,Toxicity related to previous MDS treatment must be restored to level 2 or below.

Exclusion Criteria:

The researchers determined that patients who are not suitable to participate in this study. If a patient meets any of the following criteria, they will not be allowed to enter this study:

* The subject's previous history of anti-tumor treatment meets one of the following conditions:

  1. Individuals who have previously received mitoxantrone or mitoxantrone liposomes;
  2. Previously received treatment with doxorubicin or other anthracyclines, with a total cumulative dose of doxorubicin\>360mg/m2 (1mg of doxorubicin is equivalent to 2mg of doxorubicin or 0.5mg of doxorubicin);
  3. Within 4 weeks prior to the first use of the study drug or within 5 half-lives of the drug, the patient has received anti-tumor treatment including surgery, chemotherapy, targeted therapy, or participated in other clinical trials and received clinical trial medication;
* Heart function and disease meet one of the following conditions:

  1. Long QTc syndrome or QTc interval\>480ms;
  2. Complete left bundle branch block, II or III degree atrioventricular block;
  3. Severe and uncontrolled arrhythmias that require medication treatment;
  4. The New York College of Cardiology in the United States has a classification of ≥ II;
  5. Cardiac ejection fraction (LVEF) below 50%;
  6. A history of myocardial infarction, unstable angina, severe unstable ventricular arrhythmias, or any other arrhythmias requiring treatment, a history of clinically severe pericardial disease, or evidence of acute ischemic or active conduction system abnormalities on electrocardiogram within the 6 months prior to recruitment.
* Patients who have previously or currently suffered from other malignant tumors (except for effectively controlled non melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ, and other malignant tumors that have not been treated for more than 6 months and have been effectively controlled, as well as patients who have received long-term non chemotherapy treatments such as hormone therapy);
* Uncontrollable systemic diseases (such as infection during the promotion period, uncontrollable hypertension, diabetes, etc.);
* Central nervous system leukemia;
* Secondary AML patients with bone marrow fibrosis ≥ grade 3;
* CML patients with sudden changes;
* Accompanied by a well prognosis chromosome karyotype t (8; 21) (q22; q22.1) RUNX1:: RUNX1T1, inv (16) (p13.1 q22) CBFB: MYH11, as well as acute promyelocytic leukemia;
* Human immunodeficiency virus (HIV) infected individuals (HIV antibody positive);
* Active infection of hepatitis B and hepatitis C (if hepatitis B B surface antigen or core antibody is positive, HBV-DNA will be tested additionally, and if HBV-DNA exceeds 1x103 copies/mL, it will be excluded; if hepatitis C antibody is positive, HCV-RNA will be tested additionally, and if hepatitis C virus RNA exceeds 1x103 copies/mL, it will be excluded);
* Have a known history of immediate or delayed hypersensitivity reactions to similar drugs and excipients in the study drug;
* Accompanied by a history of severe neurological or mental illness;
* The researchers determined that there were patients who were not suitable to participate in this study.

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: sujiang Zhang, Doctor — Hematological Depaement, Ruijin Hospital
• Study coordinator: Xiaoqian Xu, Doctor

Conditions Recurrent Adult Acute Myeloid Leukemia; Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia; Mitoxantrone Hydrochloride Liposomes; Cytarabine; Venetoclax; MDS-EB-2