The purpose of this prospective, multi-center, single-arm, phase 2 study is to evaluate the efficacy and safety of a combination regimen of mitoxantrone hydrochloride liposome injection, standard-dose of cytarabine and venetoclax (MAV) in the treatment of relapsed or refractory (R/R) AML. The study plan to enroll 72 R/R AML patients who are expected to receive laboratory tests of bone marrow and blood specimens at regular times after MAV treatment.
For patients with R/R AML, there is currently no established standard treatment. Previous research suggests that mitoxantrone could against venetoclax-resistant leukemia stem cells (LSCs) by modulating mitochondrial calcium levels. Based on the potentially synergistic killing effect of mitoxantrone and venetoclax, a phase 2 study is underway in R/R AML. Patients receive mitoxantrone hydrochloride liposome, moderate-dose of cytarabine (1.0 g/m\^2, IV, q12h, d1, 3, 5) and venetoclax (MAV) when they were enrolled. Here the investigator also conduct another phase 2 study of MAV regimen with standard-dose of cytarabine in relapsed or refractory (R/R) AML, aiming to evaluate the efficacy and safety of MAV regimen. All participants will receive MAV treatment including 30 mg/m\^2 mitoxantrone hydrochloride liposome on day 1, 100 mg/m\^2 cytarabine on days 1-7 and 400 mg venetoclax on days 2-8 with a dose escalation on days 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
72
Mitoxantrone hydrochloride liposome (30 mg/m\^2) on day 1, every 4 weeks
Cytarabine (100 mg/m\^2 ) on day 1-7, every 4 weeks
Venetoclax 100 mg on day 2,200 mg on day 3,400 mg on day 4-8, every 4 weeks
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGComposite complete remission (CRc) rate
Complete remission plus complete remission with incomplete hematologic recovery (CR+CRi). 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
Overall response rate (ORR)
CR+CRi+morphologic leukemia-free state+partial remission (CR+CRi+MLFS+PR). 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 the study. 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 the study. Measured from day 1 of treatment to the date of death from any cause.
Time frame: up to 12 months
Rate of CR/CRi without minimal residual disease
Percentage of participants who achieve a CR MRD-/CRi MRD- as defined by investigators based on ELN 2022 criteria. MRD level is detected by flow cytometry and negtive MRD is defined as MRD value \<0.1%.
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 which including hematologic and non-hematologic toxicity.
Time frame: From day 1 of treatment to 28 days after the last dose
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