Intermediate-dose HAD Regimen for CEBPA Double-mutated AML

Institute of Hematology & Blood Diseases Hospital, China148 enrolled

Overview

AML is highly heterogeneous in pathogenesis, and CEBPA double-mutated (CEBPAdm) AML is a common type of leukemia in China. Currently, no targeted therapies for CEBPAdm, and chemotherapy and transplantation are still the treatment options for CEBPA double-mutated AML. At present, the "3+7" treatment induction regimen of cytarabine combined with anthracyclines is still the first-line recommended regimen. In our retrospective study, the intermediate dose HAD regimen produced a 3-year RFS of 84.7% and a 3-year OS of 92.8% in CEBPAdm AML. Therefore, this project intends to confirm the efficacy of intermediate-dose HAD in the treatment of CEBPA double-mutated AML is superior to the conventional treatment regimen through the multi-center RCT study.

This is a prospective, randomized, controlled clinical trial of patients diagnosed with CEBPA double-mutated AML. Patients who meet the inclusion criteria are randomly assigned to receive the intermediate-dose HAD regimen or the conventional 3+7 induction regimen (IA or DA), respectively. When patients reach complete remission (CR) after the induction therapy, 3 courses of the high-dose cytarabine regimen (3g/m2 q12h, 3 days) are used. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment. When patients do not achieve CR after the induction therapy, reinduction therapy with IAC (IDA 10mg/ m2 for 3 days, cytarabine 100mg/m2 for 7 days, cyclophosphamide 350mg/m2 d2, d5) regimen is used. Patients who still do not achieve CR after reinduction therapy will be removed from the group.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

148

Conditions

Interventions

HADDRUG

Induction therapy:Homoharringtonine: 2mg/㎡/d, days 1-7 Cytarabine: (Ara-c 100mg/㎡/d, day 1-4; 1g/㎡ /q12h, day 5-7), Daunorubicin: (DNR 40mg/㎡/d, day 1-3). Reinduction therapy: Idarubicin (IDA) 10mg/㎡ for d1-3 , Ara-c 100mg/㎡ d1-7 , Cyclophosphamide (CTX350mg/㎡ d2, d5) . Patients who did not achieve CR after reinduction therapy were removed from the group. After achieving CR, they received high-dose cytarabine (3g/m2 q12h, 3 days) regimen for consolidation for 3 courses. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment.

Daunorubicin+CytarabineDRUG

Cytarabine: (Ara-c 100mg/㎡/d, day 1-7), Daunorubicin: (DNR 60mg/㎡/d, day 1-3) or idarubicin (IDA 12mg/㎡/d, day 1-3). Treatment did not achieve CR, and reinduction of IAC regimen was given. Reinduction therapy: Idarubicin (IDA) 10mg/㎡ ,d1-3, Ara-c 100mg/㎡ d1-7 , Cyclophosphamide (CTX350mg/㎡ d2, d5). Patients who did not achieve CR after reinduction therapy were removed from the group. After achieving CR, they received high-dose cytarabine (3g/m2 q12h, 3 days) regimen for consolidation for 3 courses. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment.

Eligibility

Sex: ALLMin age: 14 YearsMax age: 54 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. AML diagnosed according to WHO-2022 classification with recurrent CEBPA mutations and containing mutation in the bZIP domain. 2. Older than 14 years old and younger than 55 years old 3. Male or female. 4. The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of AML patients were 0-2 points. 5. Meet the following laboratory tests (performed within 7 days prior to treatment) 1) Total bilirubin ≤ 1.5 times of the upper limit of normal value (same age); 2) AST and ALT≤ 2.5 times of the upper limit of normal value (same age); 3) Blood creatinine \< 2 times of the upper limit of normal value (same age); 4) Myocardial enzymes \< 2 times of the upper limit of normal value (same age); 5) Echocardiography (ECHO) was performed to determine the ejection fraction of the heart within the normal range. Exclusion Criteria: 1. Patients who have previously received induction chemotherapy, regardless of efficacy. 2. Simultaneously suffering from malignant tumors of other organs and requiring treatment). 3. Pregnant or lactating women. Male or female patients participating in the trial must take contraceptive measures during the trial treatment period. 4. Active heart disease, defined as one or more of the following:1) Have a history of uncontrolled or symptomatic angina pectoris;2) Myocardial infarction less than 6 months prior to enrollment in the study;3) A history of arrhythmia requiring medication treatment or severe clinical symptoms;4) Uncontrolled or symptomatic congestive heart failure (\> NYHA grade 2);5) The ejection fraction is below the lower limit of the normal range. 5. Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis). 6. Those who were not considered suitable for inclusion by the researchers.

Outcomes

Primary Outcomes

Event-free survival (EFS)

The interval from randomization to assessment of response after the second course of chemotherapy treatment if patients failed to achieve CR after two courses of induction therapy, the date of relapse, or the date of death, whichever occurred first.

Time frame: up to 2 years after the date of the last enrolled participants

Secondary Outcomes

Complete response rate (CR)

The proportion that reaches CR status after two courses of induction therapy. Patients should be morphologically free of leukemia, and free of extramedullary leukemia. Absolute neutrophil counts was greater than 1.0\*10\^9/L, and platelet counts was greater than 100\*10\^9/L.

Time frame: Six weeks after induction therapy

30-day mortality

Percentage of patients who died within 30 days from randomization

Time frame: Within 30 days of randomization

overall survival

The interval from the date of randomization to the date of death or the date of last follow-up for surviving patients.

Time frame: up to 2 years after the date of the last enrolled participants

Event-free survival censored at hematopoietic stem cell transplantation

Time frame: up to 2 years after the date of the last enrolled participants

Relapse free survival censored at hematopoietic stem cell transplantation

The interval from CR to the date of relapse, or the date of death, or the date of last follow-up, or the date of hematopoietic stem cell transplantation, whichever occurred first. This outcome analyze patients achieved CR in two courses induction therapy.

Time frame: up to 2 years after the date of the last enrolled participants

overall survival censored at hematopoietic stem cell transplantation

It is defined as the time from randomization to the date of death or the date of last follow-up, or the date of hematopoietic stem cell transplantation, whichever occurred first.

Time frame: up to 2 years after the date of the last enrolled participants

60-day mortality

Percentage of patients who died within 60 days from randomization

Time frame: Within 60 days of randomization

Relapse free survival(RFS)

The interval from CR to the date of relapse, or the date of death, or the date of last follow-up, whichever occurred first. This outcome analyze patients achieved CR in two courses induction therapy.

Time frame: up to 2 years after the date of the last enrolled participants

Intermediate-dose HAD Regimen for CEBPA Double-mutated AML

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts