New Double Epigenetic Regimen in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
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.
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| Placebo Comparator: Placebo+AZA+HHT+AraC+G-CSF group The patients are randomized into the group. |
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.
|
Outcome Measures
Primary Outcome Measures
- Overall response rate (ORR) [At the end of Cycle 1 (each cycle is 28 days)]
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.
- Complete remission without minimal residual disease (CR with MRD-) [At the end of Cycle 1 (each cycle is 28 days)]
If studied pretreatment, CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC
- Complete remission with incomplete hematologic recovery (CRi) [At the end of Cycle 1 (each cycle is 28 days)]
All CR criteria except for residual neutropenia (,1.0*10E9/L [1000/uL]) or thrombocytopenia (<100*10E9/L [100 000/uL])
- Morphologic leukemia-free state (MLFS) [At the end of Cycle 1 (each cycle is 28 days)]
Bone marrow blasts ,5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required
- Partial remission (PR) [At the end of Cycle 1 (each cycle is 28 days)]
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%.
Secondary Outcome Measures
- Duration of Response (DOR) [1 year]
It is measured the time from initial response to subsequent disease progression or relapse.
- Overall Survival (OS) [1 year]
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.
- Progression-Free Survival (PFS) [1 year]
It is measured from the time from randomization to progression or death.
Other Outcome Measures
- Adverse reactions in hematology [At the end of Cycle 1 (each cycle is 28 days)]
Record of adverse events in hematological system during and after CAHAG regimen induction (agranulocytosis days, PLT/RBC transfusion units).
- Nonhematological adverse reactions [At the end of Cycle 1 (each cycle is 28 days)]
Record of adverse events in other organs or systmes during and after CAHAG regimen induction (infection and organ injury).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adults aged ≥ 18 and ≤ 70 years
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Patients diagnosed with AML according to 2016 WHO myeloid malignant disease diagnosis standard (Non-APL)
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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.
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ECOG performance status score less than 3
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Expected survival time ˃ 3 months
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Patients without serious heart, lung, liver, or kidney disease
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Ability to understand and voluntarily provide informed consent
Exclusion Criteria:
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Patients who are allergic to the study drug or drugs with similar chemical structures
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Pregnant or lactating women, and women of childbearing age who do not want to practice effective methods of contraception
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Active infection
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Active bleeding
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Patients with new thrombosis, embolism, cerebral hemorrhage, or other diseases or a medical history within one year before enrollment
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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
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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)
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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
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Surgery on the main organs within the past six weeks
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Drug abuse or long-term alcohol abuse that would affect the evaluation results
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Patients who have received organ transplants (excepting bone marrow transplantation)
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Patients not suitable for the study according to the investigator's assessment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affliated Hospital of Soochow University | Suzhou | Jiangsu | China | 215006 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
- Ruijin Hospital
- West China Hospital
- Fujian Medical University Union Hospital
- The First Hospital of Jilin University
- Anhui Provincial Hospital
- Qilu Hospital of Shandong University
- The Affiliated Cancer Hospital of Zhengzhou University
- Shandong Provincial Hospital
- Nanfang Hospital of Southern Medical University
- First Affiliated Hospital of Harbin Medical University
- Xinqiao Hospital of Chongqing
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SZCAHAG