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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

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

NCT ID

NCT05029141

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

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

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

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

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

Learn more about this trial

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

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