Treatment of relapsed or refractory acute myeloid leukemia with a new drug combination

Clinical Study of Venetoclax Combined With Mitoxantrone Liposome in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

This study is testing a new combination of drugs to see if it can help people with relapsed or hard-to-treat acute myeloid leukemia feel better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: First Affiliated Hospital of Jinan University (Academic / other)
• Drugs / interventions: chemotherapy, doxorubicin
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05522192 on ClinicalTrials.gov

What this trial studies

This clinical study is an open-label, single-arm, phase I/II investigation focusing on the treatment of relapsed or refractory acute myeloid leukemia (AML) using a combination of venetoclax and mitoxantrone liposome. The phase I component aims to determine the maximum tolerated dose (MTD) of mitoxantrone liposome, while the phase II component will evaluate the efficacy of this combination therapy across different gene mutations in AML patients. The study involves a multi-center approach with a structured treatment and follow-up period to assess patient outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are patients diagnosed with relapsed or refractory acute myeloid leukemia who meet specific inclusion criteria.

Not a fit: Patients with AML who are not relapsed or refractory, or those with significant comorbidities affecting treatment tolerance, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with relapsed or refractory acute myeloid leukemia.

How similar studies have performed: Other studies have shown promise with similar drug combinations in treating AML, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. AML confirmed by bone marrow cytology and pathology;
2. Meet the diagnostic criteria for relapsed and refractory AML. Diagnostic criteria for relapsed AML: leukemia cells reappeared in peripheral blood after complete remission or blast cells in bone marrow \>0.05 (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration. Diagnostic criteria for refractory AML: naive patients who were ineffective after 2 courses of standard regimens; patients who relapsed within 12 months after consolidation and intensive therapy after CR; patients who relapsed after 12 months but were ineffective after conventional chemotherapy; 2 or more Secondary relapse; persistent extramedullary leukemia;
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
4. Liver and kidney function: Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) (≤5 x ULN for patients with liver infiltrates); Total bilirubin ≤1.5 x ULN (≤3 x ULN for patients with liver infiltration); Serum creatinine ≤1.5 x ULN;
5. Normal cardiac function: left ventricular ejection fraction (LVEF) ≥ 45% assessed by echocardiography or radionuclide active angiography (MUGA);
6. Pulmonary function: dyspnea ≤ CTC AE grade 1 and SaO2 ≥ 92% in indoor air environment;
7. The expected survival time is greater than 3 months;
8. Patients voluntarily participated in this study and signed the informed consent.

Exclusion Criteria:

1. The subject had previously received any of the following anti-tumor treatments: a)Those who have previously received mitoxantrone or mitoxantrone liposome; b)Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin is more than 360 mg/m\^2 (1 mg doxorubicin converted from other anthracycline drugs is equivalent to 2 mg daunorubicin or 0.5 mg idarubicin); c)Have received anti-tumor treatment (including chemotherapy, targeted therapy, hormone therapy, taking traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received clinical trial drugs within 4 weeks before the first use of the study drugs;
2. Heart function and disease meet one of the following conditions: a)Long QTc syndrome or QTc interval \> 480 ms; b)Complete left bundle branch block, grade II or III atrioventricular block; c)Serious and uncontrolled arrhythmias requiring drug treatment; d)New York Heart Association grade ≥ II; e)A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.
3. Identify patients with central nervous system invasion;
4. Other malignancies, except for effectively controlled non melanoma skin basal cell carcinoma, breast / cervical carcinoma in situ, and other malignancies that have been effectively controlled without treatment in the past five years;
5. Non controlled systemic diseases (such as active infection, non controlled hypertension, diabetes, etc.);
6. Human immunodeficiency virus (HIV) infection (HIV antibody positive);
7. Active hepatitis B and C infection (hepatitis B test: if there is a positive hepatitis B surface antigen or core antibody, add HBV DNA, and the hepatitis B virus DNA exceeds 1x10\^3 copies/mL to exclude; hepatitis C: if the hepatitis C antibody is positive, further test HCV RNA, hepatitis C Viral RNA exceeding 1x10\^3 copies/mL was excluded);
8. Hypersensitivity to any study drug or its components;
9. Pregnant women, lactating women, patients who refused to take effective contraceptive measures during the study;
10. Serious neurological or psychiatric history;
11. Unsuitable subjects for this study determined by the investigator.

Where this trial is running

Guangzhou, Guangdong

• First Affiliated Hospital of Jinan University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Hui Zeng, M.D — First Affiliated Hospital of Jinan University
• Study coordinator: Hui Zeng, M.D

Conditions Relapsed or Refractory Acute Myeloid Leukemia; venetoclax; Mitoxantrone liposomes; Acute myeloid leukemia