Study of DAC Combined With HAAG Regimen in Newly Diagnosed Younger AML Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of DAC combined with HAAG regimen in the induction treatment of newly diagnosed AML patients younger than 60 years.

Detailed Description
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This is a phase 3, randomized, controlled, multi-center study in newly diagnosed AML patients younger than 60. The patients will be randomized to receive either DAC combined with HAAG or IA regimen in the induction treatment.

Official Title
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A Phase 3, Randomized, Controlled, Multi-Center Study to Evaluate the Efficacy and Safety of Decitabine Combined With HAAG Regimen in Newly Diagnosed Acute Myeloid Leukemia Patients Younger Than 60 Years

Conditions
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Acute Myeloid Leukemia, Induction Chemotherapy

Intervention / Treatment
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* Drug: Decitabine plus HAAG regimen
* Drug: Idarubicine plus Cytarabine regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed AML according to the WHO (2016) classification of acute myeloid leukemia. Age 18-59. ECOG score: 0-2. Treatment related or secondary AML. No history of previous chemotherapy or target therapy. Provide informed consent. Exclusion Criteria: Patients are pregnant or lactating. Patients have acute promylocytic leukemia or chronic myeloid leukemia in blast crisis. Patients with another malignant disease. Patients with uncontrolled active infection. Patients with left ventricular ejection fraction < 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification. Patients with aspartate aminotransferase or glutamic-pyruvic transaminase > 3x upper limit of normal or bilirubin > 2.0 mg/dL. Patients with creatinine clearance rate < 50ml/min. Patients with active hepatitis B or hepatitis C infection. Patients with HIV infection. Patients with other commodities that the investigators considered not suitable for the enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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: Decitabine combined with HAAG<br>This cohort will determine the safety and efficacy of decitabine combined with HAAG regimen in the newly diagnosed AML patients younger than 60. | Drug: Decitabine plus HAAG regimen<br>* Decitabine:20mg/m2/d,d1 5, intravenous infusion; Homoharringtonine:1mg/d,d3 16,intravenous infusion; Aclarubicin:10mg/d, d3 d10, intravenous infusion; Cytarabine:10mg/m2,q12h,d3-16, subcutaneous injection; Granulocyte colony-stimulating factor (G-CSF): 50-300μg/d (when WBC counts are less than 20×10^9/L ),subcutaneous injection;<br>|
| Active Comparator: IA Regimen<br>This cohort will determine the safety and efficacy of decitabine combined with HAAG regimen in the newly diagnosed AML patients younger than 60. | Drug: Idarubicine plus Cytarabine regimen<br>* Idarubicine :12mg/m2, d1-3, intravenous infusion; Cytarabine :100mg/m2, d1-7, 24-hours continuous intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR includes complete response (CR), CRi and PR. CR was defined as < 5% bone marrow blasts in an aspirate with spicules, no blasts with Auer rods or persistence of extramedullary disease, and independent of transfusions; CRi: was defined as<5% bone marrow blasts, either ANC<1×10^9/L or platelets<100×10^9/L, transfusion independence but with persistence of cytopenia; PR was defined as decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow aspirate and the normalization of blood counts. | Day 28-35 of induction course | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | time from randomization to death from any cause | 3 years | 
| Leukemia-free survival (LFS) | time from randomization to the first relapse or death | 3 years | 
| Cumulative incidence of relapse(CIR) | time from achievement of a remmission to the first relapse | 3 years | 
| Number of adverse events | adverse events are evaluated with CTCAE V5.0. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Decitabine, HAAG, AML