Combination treatment for relapsed or refractory acute myeloid leukemia

A Phase II Study of the Safety and Efficacy of Mitoxantrone Hydrochloride Liposome Injection, Cytarabine and Venetoclax in Patients With Relapsed/Refractory AML

This study is testing a new combination of medications to see if it can help people with relapsed or refractory acute myeloid leukemia achieve complete remission better than current treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: First Affiliated Hospital of Zhejiang University (other)
• Drugs / interventions: chemotherapy, doxorubicin
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06434662 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of a combination regimen involving mitoxantrone hydrochloride liposome injection, cytarabine, and venetoclax in patients with relapsed or refractory acute myeloid leukemia (R/R AML). It aims to determine whether this combination enhances the rate of complete remission compared to existing treatments. Participants will undergo regular laboratory tests of bone marrow and blood specimens to monitor treatment effects. The study is a single-center, single-arm, phase II trial, with a maximum of two treatment cycles planned.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with clinically diagnosed relapsed or refractory AML, excluding acute promyelocytic leukemia.

Not a fit: Patients with acute promyelocytic leukemia or those unable to tolerate intensive chemotherapy may not benefit from this study.

Why it matters

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

How similar studies have performed: Other studies have explored similar combination therapies in AML, showing promising results, but this specific combination is relatively novel.

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. Initial treatment patients who failed after 2 courses of treatment with standard regimen.
   2. Bone marrow blasts≥5% after the first 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 without treatment.
   3. First conversion from MRD negativity to MRD positivity without treatment.
4. Physical status score of Eastern Oncology Collaboration Group (ECOG) : 0-2.
5. Researchers determined that the patients could tolerate intensive chemotherapy.
6. Life expectancy \> 3 months.
7. 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. 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≥3;
   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.
3. Central nervous system leukemia;
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. A history of immediate or delayed allergy to similar drug and excipients of the investigate drug.
9. Pregnant, lactating female or subjects who refuse to use effective contraception during the study.
10. With a history of severe neurological or psychiatric illness.
11. 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

• Principal investigator: Jie Jin, M.D. — Zhejiang University
• Study coordinator: Jie Jin, M.D.

Conditions: Relapsed/Refractory Acute Myeloid Leukaemia, Myeloid Malignancy