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

Primary Purpose

Acute Myeloid Leukemia, Refractory Acute Leukemia, Relapsed Adult AML

Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
CAHAG regimen
Placebo regimen
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring chidamide, Azacitidine, priming regimen

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The First Affliated Hospital of Soochow University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

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

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

Arm Description

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.

The patients are randomized into the group.

Outcomes

Primary Outcome Measures

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.
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
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])
Morphologic leukemia-free state (MLFS)
Bone marrow blasts ,5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required
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%.

Secondary Outcome Measures

Duration of Response (DOR)
It is measured the time from initial response to subsequent disease progression or relapse.
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.
Progression-Free Survival (PFS)
It is measured from the time from randomization to progression or death.

Full Information

First Posted
August 16, 2021
Last Updated
February 12, 2023
Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
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, Southern Medical University, First Affiliated Hospital of Harbin Medical University, Xinqiao Hospital of Chongqing
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1. Study Identification

Unique Protocol Identification Number
NCT05029141
Brief Title
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

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 1, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
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, Southern Medical University, First Affiliated Hospital of Harbin Medical University, Xinqiao Hospital of Chongqing

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Refractory Acute Leukemia, Relapsed Adult AML
Keywords
chidamide, Azacitidine, priming regimen

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chidamide+AZA+HHT+AraC+G-CSF group
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo+AZA+HHT+AraC+G-CSF group
Arm Type
Placebo Comparator
Arm Description
The patients are randomized into the group.
Intervention Type
Drug
Intervention Name(s)
CAHAG regimen
Intervention Description
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
Intervention Name(s)
Placebo regimen
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
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.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Complete remission without minimal residual disease (CR with MRD-)
Description
If studied pretreatment, CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Complete remission with incomplete hematologic recovery (CRi)
Description
All CR criteria except for residual neutropenia (,1.0*10E9/L [1000/uL]) or thrombocytopenia (<100*10E9/L [100 000/uL])
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Morphologic leukemia-free state (MLFS)
Description
Bone marrow blasts ,5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Partial remission (PR)
Description
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%.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
It is measured the time from initial response to subsequent disease progression or relapse.
Time Frame
1 year
Title
Overall Survival (OS)
Description
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.
Time Frame
1 year
Title
Progression-Free Survival (PFS)
Description
It is measured from the time from randomization to progression or death.
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Adverse reactions in hematology
Description
Record of adverse events in hematological system during and after CAHAG regimen induction (agranulocytosis days, PLT/RBC transfusion units).
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Nonhematological adverse reactions
Description
Record of adverse events in other organs or systmes during and after CAHAG regimen induction (infection and organ injury).
Time Frame
At the end of Cycle 1 (each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
The First Affliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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