Clinical trial NCT05029141: New Double Epigenetic Regimen in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Refractory Acute Leukemia
Relapsed Adult AML
Keywords: chidamide
Azacitidine
priming regimen
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: Ruijin Hospital
name: West China Hospital
name: Fujian Medical University Union Hospital
name: The First Hospital of Jilin University
name: Anhui Provincial Hospital
name: Qilu Hospital of Shandong University
name: The Affiliated Cancer Hospital of Zhengzhou University
name: Shandong Provincial Hospital
name: Nanfang Hospital, Southern Medical University
name: First Affiliated Hospital of Harbin Medical University
name: Xinqiao Hospital of Chongqing
First posted: 2021-08-31
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Complete remission without minimal residual disease (CR with MRD-)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Complete remission with incomplete hematologic recovery (CRi)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Morphologic leukemia-free state (MLFS)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Partial remission (PR)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Progression-Free Survival (PFS)
timeFrame: 1 year
Other outcomes:
measure: Adverse reactions in hematology
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Nonhematological adverse reactions
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Locations:
city: Suzhou
country: China
facility: The First Affliated Hospital of Soochow University
state: Jiangsu
Study officials:
References: