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

NCT ID: NCT05029141

Last Updated: 2025-02-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2027-08-31

Brief Summary

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

Conditions

Acute Myeloid Leukemia; Refractory Acute Leukemia; Relapsed Adult AML

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chidamide+AZA+HHT+AraC+G-CSF group

The patients are randomized into the group. Patients whose last induction failure regimen is a demethylated agent combined with priming regimen enter the experimental group directly.

Group Type: EXPERIMENTAL

CAHAG regimen

Intervention Type: DRUG

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+AZA+HHT+AraC+G-CSF group

The patients are randomized into the group.

Group Type: PLACEBO_COMPARATOR

Placebo regimen

Intervention Type: DRUG

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.

Interventions

CAHAG regimen

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.

Intervention Type: DRUG

Placebo regimen

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: collaborator

West China Hospital

OTHER

Sponsor Role: collaborator

Fujian Medical University Union Hospital

OTHER

Sponsor Role: collaborator

The First Hospital of Jilin University

OTHER

Sponsor Role: collaborator

Anhui Provincial Hospital

OTHER_GOV

Sponsor Role: collaborator

Qilu Hospital of Shandong University

OTHER

Sponsor Role: collaborator

The Affiliated Cancer Hospital of Zhengzhou University

UNKNOWN

Sponsor Role: collaborator

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role: collaborator

Xinqiao Hospital of Chongqing

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Sheng-Li Xue, MD

accociate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affliated Hospital of Soochow University

Suzhou, Jiangsu, China

Countries

China

Other Identifiers

SZCAHAG

Identifier Type: -

Identifier Source: org_study_id