About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

AML diagnosed according to WHO-2022 classification with recurrent CEBPA mutations and containing mutation in the bZIP domain.

Older than 14 years old and younger than 55 years old

Male or female.

The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of AML patients were 0-2 points.

Disqualifiers

Patients who have previously received induction chemotherapy, regardless of efficacy.

Simultaneously suffering from malignant tumors of other organs and requiring treatment).

Pregnant or lactating women. Male or female patients participating in the trial must take contraceptive measures during the trial treatment period.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

HAD
Drug
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+Cytarabine
Drug
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.

Treatment groups

148 Participants

are divided into 2 treatment groups

Group A: intermediate-dose HAD regimenExperimental treatment 1 intervention

Group B: conventional treatmentActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

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

1

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

2

30-day mortality

Percentage of patients who died within 30 days from randomization

Time frame

Within 30 days of randomization

3

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

4

Event-free survival censored at hematopoietic stem cell transplantation

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, 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

Intermediate-dose HAD Regimen for CEBPA Double-mutated AML

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts