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

NCT05029141 | Active Not Recruiting Phase 2

• 1 other identifier: SZCAHAG
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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

Keywords

chidamide; Azacitidine; priming regimen

Outcome Measures

Primary Outcomes (5)

• 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.

  At the end of Cycle 1 (each cycle is 28 days)

• Complete remission without minimal residual disease (CR with MRD-)

  If studied pretreatment, CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC

  At the end of Cycle 1 (each cycle is 28 days)

• Complete remission with incomplete hematologic recovery (CRi)

  All CR criteria except for residual neutropenia (,1.0\*10E9/L \[1000/uL\]) or thrombocytopenia (\<100\*10E9/L \[100 000/uL\])

  At the end of Cycle 1 (each cycle is 28 days)

• Morphologic leukemia-free state (MLFS)

  Bone marrow blasts ,5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required

  At the end of Cycle 1 (each cycle is 28 days)

• Partial remission (PR)

  All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (3)

• Duration of Response (DOR)

  1 year

• Overall Survival (OS)

  1 year

• Progression-Free Survival (PFS)

  1 year

Other Outcomes (2)

• Adverse reactions in hematology

  At the end of Cycle 1 (each cycle is 28 days)

• Nonhematological adverse reactions

  At the end of Cycle 1 (each cycle is 28 days)

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: CAHAG regimen

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

PLACEBO COMPARATOR

The patients are randomized into the group.

Drug: Placebo regimen

Interventions

CAHAG regimen 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.

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

Placebo regimen 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.

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

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: collaborator
• West China Hospital: collaborator
• Fujian Medical University Union Hospital: collaborator
• The First Hospital of Jilin University: collaborator
• Anhui Provincial Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• Shandong Provincial Hospital: collaborator
• First Affiliated Hospital of Harbin Medical University: collaborator
• Xinqiao Hospital of Chongqing: collaborator
• The First Affiliated Hospital of Soochow University: lead
• Zhengzhou University: collaborator
• Nanfang Hospital, Southern Medical University: collaborator

Study Sites (1)

The First Affliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: accociate professor

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: August 31, 2021
• Study Start: September 1, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)