Clinical trial NCT04415008: Efficacy of HAD Induction With Intensified Cytarabine in Newly-diagnosed CEBPA Double Mutated Acute Myeloid Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: CEBPA Double Mutation
Acute Myeloid Leukemia
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2020-06-04
Enrollment: 61
Sex: ALL
Minimum age (years): 14
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: event free survival
timeFrame: 5 years
measure: relapse free survival
timeFrame: 5 years
Secondary outcomes:
measure: complete remission rate
timeFrame: 2.5 years
measure: early mortality
timeFrame: 2.5 years
measure: overall survival
timeFrame: 5 years
measure: RFS cencored at stem cell transplantation
timeFrame: 5 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: HBDH
state: Tianjin
Study officials:
References: