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

Phase 2

Recruiting

• Conditions: CEBPA Double Mutation; Acute Myeloid Leukemia
• Interventions: Drug: HAD induction with intermediate dose cytarabine

• Registration Number: NCT04415008
• Lead Sponsor: wang, jianxiang

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

Study Timeline

• Study First Submitted: 2020-05-31
• Study Start: 2020-06-01
• Study First Submitted QC: 2020-06-02
• Study First Posted: 2020-06-04
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-03
• Last Update Posted: 2023-10-05
• Primary Completion: 2024-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment arm	HAD induction with intermediate dose cytarabine	prospective, open-label, multicenter,single arm

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
complete remission rate	2.5 years	incidence of complete remission after induction chemotherapy
RFS cencored at stem cell transplantation	5 years	RFS cencored at the date of stem cell transplantation
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

Trial Locations

Locations (1)

HBDH; 🇨🇳 Tianjin, Tianjin, China