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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; CEBPA Double Mutation
• Intervention / Treatment: Drug: HAD induction with intermediate dose cytarabine

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 Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • HBDH
      • Contact: Hui Wei; Phone Number: 86-22-23909020; Email: weihui@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse free survival	survival from complete remission to relapse	5 years
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

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

Collaborators and Investigators

• Sponsor: wang, jianxiang

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 31, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine
• Other Study ID Numbers: IHBD-IIT2020008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No