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

Acute Myeloid Leukemia Clinical Trial

Official title:

A Multi-center, Randomized Clinical Trial of Chidamide Combined With Azacytidine and the HAG Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05029141
• Other study ID #: SZCAHAG
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 1, 2021
• Est. completion date: August 31, 2025

Study information

• Verified date: February 2024
• Source: The First Affiliated Hospital of Soochow University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: August 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Refractory Acute Leukemia
• Relapsed Adult AML

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
China	The First Affliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (12)

Lead Sponsor

Collaborator

The First Affiliated Hospital of Soochow University

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse reactions in hematology	Record of adverse events in hematological system during and after CAHAG regimen induction (agranulocytosis days, PLT/RBC transfusion units).	At the end of Cycle 1 (each cycle is 28 days)
Other	Nonhematological adverse reactions	Record of adverse events in other organs or systmes during and after CAHAG regimen induction (infection and organ injury).	At the end of Cycle 1 (each cycle is 28 days)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Duration of Response (DOR)	It is measured the time from initial response to subsequent disease progression or relapse.	1 year
Secondary	Overall Survival (OS)	It is measured from the time of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.	1 year
Secondary	Progression-Free Survival (PFS)	It is measured from the time from randomization to progression or death.	1 year