The goal of this study is to evaluate the efficacy and safety of a combination regimen of mitoxantrone hydrochloride liposome injection, cytarabine and venetoclax (MAV) in the treatment of relapsed or refractory (R/R) AML. It will also tentatively explore the correlation between different biological characteristics and therapeutic efficacy. The main questions it aims to answer are:Dose the combination regimen of MAV enhanced the composite complete remission in R/R AML? Participants will receive laboratory tests of bone marrow and blood specimens at regular times after MAV treatment.
Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with a poor prognosis. The "3+7" regimen, combining anthracyclines with cytarabine, remains the standard treatment for first line treatment. However, about 20% of patients will develop into primary refractory disease, and more than 50% of patients who achieved complete remission will eventually relapse. For patients with R/R AML, there is currently no established standard treatment. Combining the third drugs with "3+7" regimen is one of the clinical exploration directions. The purpose of this prospective, single-center, single-arm, pahse II study is to evaluate the efficacy and safety of a combination regimen of mitoxantrone hydrochloride liposome injection, cytarabine and venetoclax in the treatment of R/R AML. All participants will receive MAV treatment including 24 mg/m2 mitoxantrone hydrochloride liposome on day 1, 1.0 g/m2 q12h cytarabine on day 1,3,5 and 400 mg venetoclax on day 2-10 with a dose escalation on day 2-4. Each cycle consists of 4 weeks. A maximum of 2 cycles of therapy are planned.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Mitoxantrone hydrochloride liposome (24 mg/m\^2) on day 1, every 4 weeks
Cytarabine (1.0 g/m\^2, q12h ) on day 1,3,5, every 4 weeks
Venetoclax 100 mg on day 2,200 mg on day 3,400 mg on day 4-10, every 4 weeks
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGComposite complete remission (CRc) rate
Blast rate lower than 5% with or without peripheral blood cell recover
Time frame: At the end of each cycle (each cycle is 28 days), up to 2 cycles
Overall response rate (ORR)
Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria
Time frame: At the end of each cycle (each cycle is 28 days), up to 2 cycles
Relapsed free survival (RFS)
Defined only for patients achieving CR or CRi; measured from the date of achievement of remission until the date of hematologic relapse or death from any cause;
Time frame: up to 12 months
Event free survival (EFS)
Defined for all patients in a trial; measured from day 1 of treatment to the date of treatment failure, hematologic relapse from CR/CRi or death from any cause, whichever occurs first;
Time frame: up to 12 months
overall survival (OS)
Defined for all patients in a trial; measured from day 1 of treatment to the date of death from any cause;
Time frame: up to 12 months
Rate of CR without minimal residual disease (CR MRD-)
Percentage of participants who achieve a CR MRD- as defined by investigators based on ELN 2022 criteria; MRD level is detected by flow cytometry which value \<0.1% is defined as negtive;
Time frame: At the end of each cycle (each cycle is 28 days), up to 2 cycles
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The safety of the drug was evaluated by NCI-CTC AE 5.0 standard.Hematologic and non-hematologic toxicity.
Time frame: From day 1 of treatment to 28 days after the last dose
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