Study on the Efficacy and Safety of VA Regimen Compared to "3+7" Regimen in Newly Diagnosed AML With NPM1 or IDH1/IDH2 Mutations

Official title

A Prospective, Multicenter, Randomized Controlled, Open Label, Non-Inferiority Study Comparing the Efficacy and Safety of the VA Regimen (Venetoclax Combined With Azacitidine) With the "3+7" Regimen in the Treatment of Newly Diagnosed AML Patients With NPM1 or IDH1/IDH2 Mutations

Overview

This prospective, multicenter, randomized, open-label, non-inferiority clinical study aims to compare the efficacy and safety of VA regimen (venetoclax combined with azacitidine) versus conventional "3+7" chemotherapy regimen in adult patients aged 18 to 65 years with newly diagnosed acute myeloid leukemia (AML) carrying NPM1, IDH1 or IDH2 gene mutations. The primary goal of this trial is to check whether the VA treatment can reach a non-inferior composite complete remission rate at the end of the induction treatment cycle, which is the key primary endpoint of this research. Several secondary clinical outcomes will also be evaluated in this study, including the rate of minimal residual disease (MRD) negativity after remission, duration of remission, 1-year event-free survival rate and 1-year overall survival rate of enrolled patients. In addition, the safety and treatment-related side effects occurring during the whole induction treatment phase will be systematically collected and compared between two groups as another important secondary assessment. Eligible enrolled participants will be randomly split into two study groups: patients in experimental group will receive venetoclax plus azacitidine (VA regimen), while patients in control group will receive standard "3+7" induction chemotherapy following conventional clinical protocol. All subjects will complete regular disease assessment, laboratory examinations and scheduled follow-up visits as required by trial design during treatment and post-treatment observation period. Researchers will collect and analyze all above clinical outcome data from all participants, to verify the non-inferior efficacy and relative safety of VA regimen for this specific subtype of newly diagnosed AML patients.

Interventions

• Drug VEN combined with azacitidine
  Venetoclax,oral targeted anti-BCL-2 agent and Azacitidine,hypomethylating agent, given via injection for experimental VA arm only
• Drug Cytarabine plus Daunorubicin
  Cytarabine,continuous intravenous infusion for total 7 days and Daunorubicin,Intravenous anthracycline chemotherapy administered for 3 days,in standard 3+7 induction regimen

Primary outcome measures

• Composite complete remission rate at the end of induction cycle [Time frame: At the end of 1-2 induction treatment cycles (each cycle is 28 days)]

Secondary outcome measures (7)

• Composite Complete Remission [Time frame: At the end of 1-2 induction treatment cycles (each cycle is 28 days)]
• Minimal residual disease (MRD) negative rate after remission [Time frame: At the end of induction cycle (each cycle is 28 days)]
• Duration of Response (DoR) [Time frame: From date of confirmed complete response (CR) until documented disease relapse or death from any cause, assessed up to 24 months after randomization]
• 1-year Event-Free Survival (EFS) rate [Time frame: From date of randomization until first documented treatment failure, relapse, or death from any cause, assessed up to 24 months after randomization; 1-year rate calculated at 12 months post-randomization]
• 1-year Overall Survival (OS) rate [Time frame: From date of randomization until death from any cause, assessed up to 24 months after randomization; 1-year rate calculated at 12 months post-randomization]
• 1-year recurrence free survival rate [Time frame: From date of randomization until first confirmed disease recurrence or death from any cause, assessed up to 24 months after randomization; the 1-year rate will be calculated at the 12-month timepoint after randomization]
• Safety profile during induction therapy [Time frame: From initiation of induction therapy through the end of the induction treatment period,assessed up to 8 weeks after randomization]

Eligibility criteria

Inclusion criteria

• Age ≥ 65 years old ≥ 18 years old;
• Diagnosed as acute myeloid leukemia (non APL) (diagnostic criteria refer to the 2022 ELN classification system);
• Initial diagnosis accompanied by NPM1 mutations (A, B, D types and rare types are all acceptable) and/or IDH1/IDH2 mutations;
• Have not received any other induction therapy before (except hydroxyurea);
• Physical fitness status score (ECOG PS) 0-3;
• Having sufficient organ function, defined as follows:

• Liver function: serum total bilirubin ≤ 3 x upper limit of normal range (ULN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3 x ULN, unless considered to be caused by leukemia;
• Renal function: endogenous creatinine clearance rate ≥ 30ml/min;
• Heart function: NYHA classification ≤ 2 points;
• Participants must have the ability to understand and be willing to participate in this study, and sign an informed consent form.

Exclusion criteria

• Acute promyelocytic leukemia;
• Merge extramedullary infiltration such as central nervous system leukemia;
• Have a clear history of CMML or MDS, and later progress to AML; Or have a history of malignant tumors;
• There is uncontrolled active infection (including bacterial, fungal, or viral infections);
• Pregnant or lactating women;
• Researchers determine that participants are not suitable to participate in this experiment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT07664839 · NPM1/IDH-AML01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗