Optimizing Induction Chemotherapy Regimens for ND Elderly AML Patients Who Are Eligible for Intense Chemotherapy

Study Overview
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Brief Summary
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The optimal induction chemotherapy regimen for newly diagnosed elderly AML patients who are eligible for intense chemotherapy is currently not well defined. Thus, we intend to conduct a multicenter, randomized, controlled clinical trial to compare the safety and efficacy of three different induction regimens (Ven+AZA vs DA/IA 3+7 vs DA/IA 2+5+VEN). A total of 90 patients will be enrolled in this study and segregated into thress groups with 30 in each group. Patients who achieve CR/CRi/CRh after using different induction regimens will receive the same consolidation and maintenance therapy. Allogeneic hematopoietic stem cell transplantation is recommended for patients in the high-risk group or those with persist MRD positivity. After completion of the treatment phase, patients entered the follow-up period.

Official Title
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Optimizing Induction Chemotherapy Regimens for Newly Diagnosed Elderly Acute Myeloid Leukemia Patients Who Are Eligible for Intense Chemotherapy: A Multicenter, Randomized, Controlled Phase II Clinical Trial

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Other: Different induction chemotherapy regimens


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand the study and voluntarily sign informed consent. Age: 60 75 years old, gender unlimited. Patients diagnosed with acute myeloid leukemia according to The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia who haven't been treated. Eastern Cooperative Oncology Group (ECOG) physical state score: 0-2. Fit for intensive chemotherapy. The function of main organs should meet the following standards before treatment: Kidney: serum creatinine ≤ 2× upper limit of normal range (ULN); Liver: total bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5× ULN; Heart: myocardial enzymes ≤ 2× ULN and normal ejection fraction by cardiac color doppler ultrasound Exclusion Criteria: Patients with acute promyelocytic leukemia Patients with RUNX1::RUNX1T1 or CBFB::MYH11 fusion gene Patients with BCR::ABL fusion gene Patients who have received a prior treatment for AML with chemotherapy, hypomethylating agents or venetoclax before. Patients with concurrent malignant tumors requiring treatment Patients with active heart disease defined as one or more of the following: (1) Uncontrolled or symptomatic angina pectoris;(2) A myocardial infarction 6 months before enrolled; (3)Arrhythmia needed medication or with severe clinical symptoms;(4)Uncontrolled or symptomatic congestive heart failure (NYHA> grade 2);(5)Left ventricular ejection fraction below the lower limit of the normal range. Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZA+VEN<br>Two courses of azacitidine combined with venetoclax as induction regimen | Other: Different induction chemotherapy regimens<br>* azacitidine combined with venetoclax or chemotherapy with or without venetoclax<br>|
| Experimental: DA/IA 3+7<br>Daunorubicin or Idarubicin ×3 days combined with cytarabine × 7 days as induction regimen | Other: Different induction chemotherapy regimens<br>* azacitidine combined with venetoclax or chemotherapy with or without venetoclax<br>|
| Experimental: DA/IA 2+5+VEN<br>Daunorubicin or Idarubicin ×2 days, cytarabine × 5 days combined with venetoclax as induction regimen | Other: Different induction chemotherapy regimens<br>* azacitidine combined with venetoclax or chemotherapy with or without venetoclax<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival (EFS) | It is defined as the time from the start of randomization to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first). | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission (CR) rate or complete remission with partial hematologic recovery (CRh) rate or complete remission with incomplete hematologic recovery (CRi) rate | Proportion of patients with CR, CRh or CRi | Up to approximately eight weeks | 
| Minimal residual disease (MRD)-negative remission rates after induction | Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative | Up to approximately eight weeks | 
| Cumulative incidence of minimal residual disease (MRD)-negative remission rates | The proportion of patients with negative MRD results at any time during treatment | Up to approximately 1 years | 
| Relapse-free Survival (RFS) | It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up. | Up to approximately 2 years | 
| Overall survival (OS) | It is defined as the time from the start of randomization to the death from any cause. | Up to approximately 2 years | 
| 30-day postinduction mortality | It is defined as death from any cause within 30 days after the start of induction. | Up to approximately 30 days | 
| 60-day postinduction mortality | It is defined as death from any cause within 60 days after the start of induction. | Up to approximately 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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elderly, newly diagnosed, fit, induction regimen