Acute Myeloid Leukemia, CEBPA Double Mutation
Conditions
Brief summary
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
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
Interventions
DRUGHAD induction with intermediate dose cytarabine
daunorubicin,cytarabine,homoharringtonine
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 55 Years
Healthy volunteers
No
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） 1. serum total bilirubin≤1.5xULN； 2. serum AST and ALT≤2.5xULN 3. serum creatinine≤2xULN； 4. cardiac enzymes≤2xULN 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| event free survival | 5 years | Measured from day 1 of randomization to the date of treatment failure, hematologic relapse from CR or death from any cause, whichever occurs first |
| relapse free survival | 5 years | survival from complete remission to relapse |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| complete remission rate | 2.5 years | incidence of complete remission after induction chemotherapy |
| early mortality | 2.5 years | death during 30 days from induction chemotherapy |
| overall survival | 5 years | duration from enrollment to death or loss of followup |
| RFS cencored at stem cell transplantation | 5 years | RFS cencored at the date of stem cell transplantation |
Countries
China
Outcome results
None listed