New Double Epigenetic Regimen in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Phase 2Active Not RecruitingNCT05029141

The First Affiliated Hospital of Soochow University21 enrolled

Overview

This study is to investigate the therapeutic efficacy and side effect of chidamide, azacitidine combined with priming HAG regimen for relapsed or refractroy acute myeloid leukemia

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia Refractory Acute Leukemia Relapsed Adult AML

Interventions

CAHAG regimenDRUG

Chidamide 30mg orally twice every week for 2 weeks on days 1, 4, 8, 11, azacytidine 75mg/m2 intravenously daily for 7 days (d3-d9) and HAG regimen (cytarabine, 10 mg/m2 subcutaneously every 12 h on days 3-16; homoharringtonine, 1mg/m2 intravenously every day on days 3-16; and concurrent granulocyte colony-stimulating factor, 200mg/m2/day subcutaneously daily from days 2 to neutral granulocyte recovery. (when WBC \> 20×10E9/L, G-CSF paused). One treatment cycle for 28 days, a total of 2 cycles. If the bone marrow assessment is MLFS on the 28th day in the first cycle, the second cycle of treatment will be started after NE\<1.0×10E9/L; if the delay exceeds 2 weeks, the patient needs to withdraw from the trial.

Placebo regimenDRUG

Chidamide 0mg orally twice every week for 2 weeks on days 1, 4, 8, 11, azacytidine 75mg/m2 intravenously daily for 7 days (d3-d9) and HAG regimen (cytarabine, 10 mg/m2 subcutaneously every 12 h on days 3-16; homoharringtonine, 1mg/m2 intravenously every day on days 3-16; and concurrent granulocyte colony-stimulating factor, 200mg/m2/day subcutaneously daily from days 2 to neutral granulocyte recovery. (when WBC \> 20×10E9/L, G-CSF paused). One treatment cycle for 28 days, a total of 2 cycles. If the bone marrow assessment is MLFS on the 28th day in the first cycle, the second cycle of treatment will be started after NE\<1.0×10E9/L; if the delay exceeds 2 weeks, the patient needs to withdraw from the trial.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 69 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults aged ≥ 18 and ≤ 70 years * Patients diagnosed with AML according to 2016 WHO myeloid malignant disease diagnosis standard (Non-APL) * Patients with AML must meet one of the following criteria, A or B: A: Refractory AML disease was defined as follows: (1) failure to attain CR following exposure to at least 2 courses of standard or intensive induction therapy; or (2) bone marrow leukemia cell decline index (BMCDI) \< 50% and \> 20% after 1 course of standard or intensive induction therapy. B: Relapsed AML disease was defined as follows: (1) reappearance of leukemic blasts in the peripheral blood after CR; or (2) detection of ≥ 5% blasts in the BM not attributable to another cause (e.g., BM regeneration after consolidation therapy); or (3) extramedullary relapse. * ECOG performance status score less than 3 * Expected survival time ˃ 3 months * Patients without serious heart, lung, liver, or kidney disease * Ability to understand and voluntarily provide informed consent Exclusion Criteria: * Patients who are allergic to the study drug or drugs with similar chemical structures * Pregnant or lactating women, and women of childbearing age who do not want to practice effective methods of contraception * Active infection * Active bleeding * Patients with new thrombosis, embolism, cerebral hemorrhage, or other diseases or a medical history within one year before enrollment * Patients with mental disorders or other conditions whereby informed consent cannot be obtained and where the requirements of the study treatment and procedures cannot be met * Liver function abnormalities (total bilirubin \> 1.5 times the upper limit of the normal range, ALT/AST \> 2.5 times the upper limit of the normal range or patients with liver involvement whose ALT/AST \> 1.5 times the upper limit of the normal range), or renal anomalies (serum creatinine \> 1.5 times the upper limit of the normal value) * Patients with a history of clinically significant QTc interval prolongation (male \> 450 ms; female \> 470 ms), ventricular heart tachycardia and atrial fibrillation, II-degree heart block, myocardial infarction attack within one year before enrollment, and congestive heart failure, and patients with coronary heart disease who have clinical symptoms and requiring drug treatment * Surgery on the main organs within the past six weeks * Drug abuse or long-term alcohol abuse that would affect the evaluation results * Patients who have received organ transplants (excepting bone marrow transplantation) * Patients not suitable for the study according to the investigator's assessment

Locations (1)

The First Affliated Hospital of Soochow University

Suzhou, Jiangsu, China

Outcomes

Primary Outcomes

Overall response rate (ORR)

The overall response (completed remission without minimal residual disease, completed remission with incomplete blood count recovery, morphologic leukemia-free state and partial remission) rate achieved after one or two courses(28 days) induction therapy by CAHAG regimen.