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

wang, jianxiang

Status and phase: Enrolling; Phase 2

Conditions: CEBPA Double Mutation; Acute Myeloid Leukemia

Treatments: Drug: HAD induction with intermediate dose cytarabine

Study type: Interventional

Funder types: Other

Identifiers

NCT04415008

IHBD-IIT2020008

Details and patient eligibility

About

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.

Full 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

Enrollment: 40 estimated patients

Sex: All

Ages: 14 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

treatment arm

Experimental group

Description:

prospective, open-label, multicenter,single arm

Treatment:

Drug: HAD induction with intermediate dose cytarabine