Intermediate-dose HAD Regimen for CEBPA Double-mutated AML (HADCEBPA2023)

Institute of Hematology & Blood Diseases Hospital, China

Status: Enrolling

Conditions: AML

Treatments: Drug: HAD; Drug: Daunorubicin+Cytarabine

Study type: Interventional

Funder types: Other

Identifiers

NCT06529250

IIT2023005

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 148 estimated patients

Sex: All

Ages: 14 to 54 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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148 participants in 2 patient groups

intermediate-dose HAD regimen

Experimental group

Description:

Patients received intermediate-dose HAD regimen. 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.

Treatment:

Drug: HAD

conventional treatment

Active Comparator group

Description:

Patients were treated with 3+7 induction regimen (IA or DA). 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.

Treatment:

Drug: Daunorubicin+Cytarabine