Efficacy of HAD Induction With Intensified Cytarabine in Newly-diagnosed CEBPA Double Mutated Acute Myeloid Leukemia

Study Overview
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Brief Summary
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Acute myeloid leukemia is a heterogenous hematological malignancy, characterized by different cytogenetic or molecular features. CEBPA double mutation acute myeloid leukemia （CEBPAdm AML）has favourite prognosis, especially in younger adult patients. But cumulative incidence of relapse of this group patients is still high, so the treatment options need to be optimized urgently.HAD(homoharringtonine(HHT)+cytarabine+daunorubicin) with intermediate dose cytarabine improved the survival of AML, especially in patients with CEBPA double mutation.

Detailed Description
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In this phase 2 study, 40 patients will be enrolled and treated with HAD induction regimen. High dose cytarabine will be given after complete remission achieved. The primary endpoint was event-free and relapse-free survival. Genetic mutations and measurable residual disease (MRD) will be detected at diagnosis and after chemotherapy. The risk stratification according to genetic mutations and MRD will also be explored. induction chemotherapy:HHT 2mg/m2/d,day 1-7 cytarabine 100mg/m2/d, day1-4；1g/m2 /q12h ，day5-7 DNR 40mg/m2/d，day 1-3 re-induction chemotherapy:IDA 10mg/m2，day 1-3 cytarabine 100mg/m2，day 1-7 CTX 350mg/m2，day 2，day 5 consolidation chemotherapy: high dose cytarabine 3g/m2/Q12h,day1-3,for three cycles

Official Title
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A Prospective, Multicenter, Single Arm Clinical Study to Evaluate Efficacy of HAD Induction With Intensified Cytarabine in Newly-diagnosed CEBPA Double Mutated Acute Myeloid Leukemia

Conditions
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CEBPA Double Mutation, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: HAD induction with intermediate dose cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly-diagnosed of acute myeloid leukemia except acute promyelocytic leukemia with CEBPA double mutation age≥ 14 years and<55 years，male or female ECOG-PS score 0-2 laboratory tests（within 7 days before chemotherapy） serum total bilirubin≤1.5xULN； serum AST and ALT≤2.5xULN serum creatinine≤2xULN； cardiac enzymes≤2xULN ejection fraction >50% by ECHO。 written informed consent。 Exclusion Criteria: subject has received remission induction chemotherapy secondary AML with other hematological malignancy with other tumors(needing treatment) pregnant or lactating women active heart diseases severe active infection unfit for enrollment evaluated by investigator

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 55 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment arm<br>prospective, open-label, multicenter,single arm | Drug: HAD induction with intermediate dose cytarabine<br>* daunorubicin,cytarabine,homoharringtonine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event free survival | Measured from day 1 of randomization to the date of treatment failure, hematologic relapse from CR or death from any cause, whichever occurs first | 5 years | 
| relapse free survival | survival from complete remission to relapse | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate | incidence of complete remission after induction chemotherapy | 2.5 years | 
| early mortality | death during 30 days from induction chemotherapy | 2.5 years | 
| overall survival | duration from enrollment to death or loss of followup | 5 years | 
| RFS cencored at stem cell transplantation | RFS cencored at the date of stem cell transplantation | 5 years |