Combination treatment for relapsed or refractory acute myeloid leukemia

A Prospective, Multi-center, Phase 2 Study of Mitoxantrone Hydrochloride Liposome Injection Combined With Standard-dose Cytarabine and Venetoclax in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

This study is testing a new combination of three medications to see if it can help people with relapsed or refractory acute myeloid leukemia feel better and improve their treatment results.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: First Affiliated Hospital of Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy, doxorubicin
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06621212 on ClinicalTrials.gov

What this trial studies

This exploratory study evaluates the efficacy and safety of a combination regimen of mitoxantrone hydrochloride liposome, standard-dose cytarabine, and venetoclax in patients with relapsed or refractory acute myeloid leukemia (R/R AML). The study aims to enroll 20 patients who will receive the MAV treatment regimen over a maximum of two cycles, with regular laboratory tests to monitor their response. The approach is based on previous findings suggesting that mitoxantrone may effectively target leukemia stem cells resistant to venetoclax, potentially enhancing treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with clinically diagnosed relapsed or refractory AML who have failed at least one prior treatment course.

Not a fit: Patients with acute promyelocytic leukemia or those with a life expectancy of less than three months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with R/R AML who currently have limited treatment choices.

How similar studies have performed: While this approach is exploratory, previous studies have indicated potential success with similar combinations in targeting resistant leukemia cells.

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
3. Clinically diagnosed relapsed/refractory AML, excluding acute promyelocytic leukemia.

   1. Patients who failed after at least 1 courses of initial induction therapy.
   2. Bone marrow blasts≥5% after CR/CRi, or reappearance of blasts in the blood in at least 2 peripheral blood samples at least one week apart, or leukemia cell infiltration appeared in extramedullary.
   3. Conversion from MRD negativity to MRD positivity after CR/CRi.
4. Physical status score of Eastern Oncology Collaboration Group (ECOG) 0-2.
5. Life expectancy \> 3 months.
6. AST/ALT≤2.5 ULN (for subjects with hepatic infiltration≤5 ULN); Total bilirubin≤1.5 ULN (for subjects with hepatic infiltration≤3 ULN); Serum creatinine≤1.5 ULN.

Exclusion Criteria:

1. Previous anti-tumor therapy meets one of the following criteria:

   1. Prior therapy with mitoxantrone or mitoxantrone liposome;
   2. Prior therapy with doxorubicin or 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. Have received other anti-tumor therapy (including chemotherapy, targeted therapy, hormone therapy, Chinese medicines with anti-tumor activity, except those that do not affect the efficacy of the study as determined by the investigator) or participated in other clinical trials and received clinical trial drugs within 4 weeks or 5 half-lives of the drug before the study;
2. Subjects who received strong or moderate CYP3A inducers/inhibitors or P-glycoprotein (P-gp) inhibitors within 7 days before starting study treatment;
3. Subjects who are unable to take oral medications or have malabsorption syndrome;
4. Cardiovascular diseases, including but not limited to:

   1. QTc interval \>480 ms or long QTc syndrome in screening;
   2. Complete left bundle branch block, 2 or 3 grade atrioventricular block;
   3. Requiring treatment of serious and uncontrolled arrhythmia;
   4. New York Heart Association NYHA≥2;
   5. Cardiac ejection fraction (EF) was less than 50%;
   6. 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.
5. Central nervous system leukemia;
6. 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).
7. Subjects are suffering from any other uncontrollable disease (including but not limited to: uncontrolled diabetes and hypertension, and advanced infection);
8. HIV infection.
9. HBsAg or HBcAb positive, with HBV-DNA≥1x10\^3 copies/mL; or HCV-RNA≥1x10\^3 copies/mL;
10. A history of immediate or delayed allergy to similar drug and excipients of the investigate drug.
11. Pregnant, lactating female or subjects who refuse to use effective contraception during the study.
12. With a history of severe neurological or psychiatric illness.
13. Not suitable for this study as decided by the investigator.

Where this trial is running

Hangzhou, Zhejiang

• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Jie Jin, M.D.

Conditions Relapsed/Refractory Acute Myeloid Leukaemia; Myeloid Malignancy