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Venetoclax+HMA+Aclarubicin Versus Venetoclax+HMA in Treatment-Naive Elderly Patients With AML

Primary Purpose

Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Venetoclax-Decitabine/Azacitidine-Aclarubicin Association
Venetoclax-Decitabine/Azacitidine Association
Sponsored by
The First Affiliated Hospital with Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

60 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients with acute myeloid leukemia (AML) diagnosed by bone marrow morphology and immunophenotyping (in line with WHO 2016 diagnostic criteria);
  2. No previous anti-acute leukemia treatment (including demethylating drugs), except hydroxyurea and Leukocyte apheresis;
  3. Exclude acute promyelocytic leukemia (APL) at the bone marrow morphology or molecular level;
  4. Age 60-80 years old;
  5. Aspartate aminotransferase (ALT), alanine aminotransferase (AST), and alkaline phosphatase (ALP)≤ 3×upper limit of normal (ULN), serum bilirubin≤ 1.5×ULN; serum creatinine≤ 2.0×ULN; serum heart rate≤ 2.0×ULN;
  6. LVEF determined by echocardiography≥ 50%;
  7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
  8. Obtain informed consent signed by the patient or legal representative.

Exclusion Criteria:

  1. Acute promyelocytic leukemia, myeloid sarcoma, accelerated phase and blast of chronic myeloid leukemia;
  2. Patients with relapsed AML;
  3. Allergy to any drug involved in the program;
  4. Pregnant, lactating women and patients of childbearing age who are unwilling to take contraceptive measures;
  5. The liver and kidney functions are obviously abnormal, exceeding the inclusion criteria;
  6. Structural heart disease, such as uncontrolled or symptomatic arrhythmia, congestive heart disease, heart failure or myocardial infarction within 6 months prior to screening, resulting in clinical symptoms or abnormal cardiac function;
  7. Suffering from other malignant tumors at the same time; except for the following cases: ①Have received treatment for the purpose of cure, and have no known active malignance for ≥5 years before enrollment; ② Adequately treated non-melanoma skin cancer or malignant lentigo with no signs of disease (even if less than 3 years before randomization); ③ Adequately treated carcinoma in situ with no signs of disease (even if less than 3 years before randomization);
  8. AIDS patients, syphilis patients, active type Hepatitis B (HBV-DNA detectable) patients, and Hepatitis C patients;
  9. Any concurrent medical condition or disease (such as active systemic infection) that may interfere with study procedures or results, or which, in the judgment of the investigator, poses a risk to participation in this study；
  10. Inability to understand or comply with the research protocol;
  11. Received major surgery within 4 weeks before randomization;
  12. Participate in other clinical investigators at the same time one month before enrollment.

Sites / Locations

  • The First Affiliated Hospital with Nanjing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Venetoclax combined with Decitabine/Azacitidine and Aclarubicin

Venetoclax combined with Decitabine/Azacitidine

Arm Description

Venetoclax (Ven): oral once daily (100 mg d1, 200 mg d2, 400 mg d3-28); Decitabine (DAC): 20mg/m2 intravenous for 1 hour daily (d1 to d5); Azacitidine (AZA): 75mg/m2 subcutaneous at two different sites daily (d1 to d7);(Choose decitabine or azacitidine according to the patient's wishes) Aclarubicin (Acla): 10mg/m2 intravenous daily (d1 to d3);

Venetoclax (Ven): oral once daily (100 mg d1, 200 mg d2, 400 mg d3-28); Decitabine (DAC): 20mg/m2 intravenous for 1 hour daily (d1 to d5); Azacitidine (AZA): 75mg/m2 subcutaneous at two different sites daily (d1 to d7);(Choose decitabine or azacitidine according to the patient's wishes)

Outcomes

Primary Outcome Measures

Percentage of participants with complete remission (CR) and complete remission with incomplete marrow recovery (CRi)
CR is defined as absolute neutrophil count > 10^9/ L, platelets > 100×10^9/L, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of < 10^9/L or platelets < 100×10^9/L.

Secondary Outcome Measures

Partial Remission (PR) Rate
PR is defined as bone marrow with 5%~25% blasts, at least 50% lower than the initial diagnosis.
Overall Response Rate (ORR)
Complete Remission/ Complete Remission with incomplete count recovery/ Partial Remission/ Morphologic Leukemia Free State
Rate of Minimal Residual Disease (MRD) negativity
Percentage of participants who converted to MRD < 10^-3 before initiation of consolidation therapy. MRD is measured by MFC and RT-qPCR.
Overall survival (OS)
It is measured from the date of randomization 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.
Disease-Free Survival (DFS)
It is defined as the time from the date of CR/CRi to the date of recurrence or death.
Early Mortality Rate
Cumulative incidence of relapse (CIR)
It is measured from the date of CR/CRi to the date of relapse.

Full Information

First Posted
February 27, 2022
Last Updated
May 26, 2023
Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
The Affiliated Jiangning Hospital of Nanjing Medical University, Huai'an First People's Hospital, Yancheng First People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05264883
Brief Title
Venetoclax+HMA+Aclarubicin Versus Venetoclax+HMA in Treatment-Naive Elderly Patients With AML
Official Title
Comparing the Efficacy and Safety of Venetoclax Combined With Decitabine/Azacitidine and Aclarubicin Versus Venetoclax Combined With Decitabine/Azacitidine in Treatment-Naive Elderly Patients With Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
June 28, 2023 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University
Collaborators
The Affiliated Jiangning Hospital of Nanjing Medical University, Huai'an First People's Hospital, Yancheng First People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This research is being done to assess the therapeutic efficacy and safety of a promising regimen (Venetoclax combined with Decitabine/Azacitidine and Aclarubicin) versus Venetoclax combined with Decitabine/Azacitidine in treatment-naive elderly patients with Acute Myeloid Leukemia. This study involves the following: Venetoclax, Decitabine/Azacitidine, Aclarubicin (investigational combination) Venetoclax and Decitabine/Azacitidine (per standard of care)
Detailed Description
This is an open-label, multicenter, phase Ⅲ randomized clinical trial to compare the therapeutic efficacy and safety of Venetoclax combined with Decitabine/Azacitidine and Aclarubicin versus Venetoclax combined with Decitabine/Azacitidine in treatment-naive elderly patients with Acute Myeloid Leukemia (AML). The FDA has approved the combination therapy of Venetoclax and Decitabine/Azacitidine for elderly (> 60-year-old) patients with newly diagnosed AML not eligible for intensive chemotherapy. Venetoclax is an inhibitor of BCL-2 (B-cell lymphoma 2, a protein that initiates tumor growth, disease progression, and drug resistance), which can lead to cancer cell death. Aclarubicin (Acla) is an anthracycline antitumor drug and is a type II topoisomerase Inhibitor that prevents topoisomerase II from binding to DNA primarily by intercalating into DNA strands, resulting in chromatin damage injury without causing DNA damage. In addition to causing chromatin damage, Acla also results in epigenetic inheritance Changes in gene transmission, DNA damage response signals, and apoptosis. Furthermore, in the cytoplasm, Acla can also exert cytotoxic effects by affecting mitochondrial respiratory function. Therefore, Acla is a highly efficient and broad-spectrum chemotherapeutic drug, which is widely used in the treatment of various hematological tumors and solid tumors. In treatment-naive elderly patients with AML, the DCAG (Decitabine-Cytarabine-Aclarubicin-GCSF) regimen can improve the prognosis according to our previous research results. Acla also has relatively mild side effects in the treatment of AML patients. Participants will be randomly assigned to one of the different treatment groups and followed with consolidated therapy with the same regimen of 2-4 cycles. After completion of study treatment, participants are followed up every 3 months for up to 2 years. It is expected that about 170 people will take part in this research study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
170 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Venetoclax combined with Decitabine/Azacitidine and Aclarubicin
Arm Type
Experimental
Arm Description
Venetoclax (Ven): oral once daily (100 mg d1, 200 mg d2, 400 mg d3-28); Decitabine (DAC): 20mg/m2 intravenous for 1 hour daily (d1 to d5); Azacitidine (AZA): 75mg/m2 subcutaneous at two different sites daily (d1 to d7);(Choose decitabine or azacitidine according to the patient's wishes) Aclarubicin (Acla): 10mg/m2 intravenous daily (d1 to d3);
Arm Title
Venetoclax combined with Decitabine/Azacitidine
Arm Type
Active Comparator
Arm Description
Venetoclax (Ven): oral once daily (100 mg d1, 200 mg d2, 400 mg d3-28); Decitabine (DAC): 20mg/m2 intravenous for 1 hour daily (d1 to d5); Azacitidine (AZA): 75mg/m2 subcutaneous at two different sites daily (d1 to d7);(Choose decitabine or azacitidine according to the patient's wishes)
Intervention Type
Drug
Intervention Name(s)
Venetoclax-Decitabine/Azacitidine-Aclarubicin Association
Intervention Description
Treatment with Venetoclax+Decitabine/Azacitidine+Aclarubicin
Intervention Type
Drug
Intervention Name(s)
Venetoclax-Decitabine/Azacitidine Association
Intervention Description
Treatment with Venetoclax+Decitabine/Azacitidine
Primary Outcome Measure Information:
Title
Percentage of participants with complete remission (CR) and complete remission with incomplete marrow recovery (CRi)
Description
CR is defined as absolute neutrophil count > 10^9/ L, platelets > 100×10^9/L, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of < 10^9/L or platelets < 100×10^9/L.
Time Frame
From randomization to the end of Cycle 1 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Partial Remission (PR) Rate
Description
PR is defined as bone marrow with 5%~25% blasts, at least 50% lower than the initial diagnosis.
Time Frame
From randomization to the end of Cycle 1 (each cycle is 28 days)
Title
Overall Response Rate (ORR)
Description
Complete Remission/ Complete Remission with incomplete count recovery/ Partial Remission/ Morphologic Leukemia Free State
Time Frame
From randomization to the end of Cycle 1 (each cycle is 28 days)
Title
Rate of Minimal Residual Disease (MRD) negativity
Description
Percentage of participants who converted to MRD < 10^-3 before initiation of consolidation therapy. MRD is measured by MFC and RT-qPCR.
Time Frame
From randomization to the end of Cycle 1 (each cycle is 28 days)
Title
Overall survival (OS)
Description
It is measured from the date of randomization 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
From the time of randomization to time for up to 2 years
Title
Disease-Free Survival (DFS)
Description
It is defined as the time from the date of CR/CRi to the date of recurrence or death.
Time Frame
From the time of randomization to time for up to 2 years
Title
Early Mortality Rate
Time Frame
From the time of randomization to time for up to 2 years
Title
Cumulative incidence of relapse (CIR)
Description
It is measured from the date of CR/CRi to the date of relapse.
Time Frame
From the time of CR/CRi to time for up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with acute myeloid leukemia (AML) diagnosed by bone marrow morphology and immunophenotyping (in line with WHO 2016 diagnostic criteria); No previous anti-acute leukemia treatment (including demethylating drugs), except hydroxyurea and Leukocyte apheresis; Exclude acute promyelocytic leukemia (APL) at the bone marrow morphology or molecular level; Age 60-80 years old; Aspartate aminotransferase (ALT), alanine aminotransferase (AST), and alkaline phosphatase (ALP)≤ 3×upper limit of normal (ULN), serum bilirubin≤ 1.5×ULN; serum creatinine≤ 2.0×ULN; serum heart rate≤ 2.0×ULN; LVEF determined by echocardiography≥ 50%; Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; Obtain informed consent signed by the patient or legal representative. Exclusion Criteria: Acute promyelocytic leukemia, myeloid sarcoma, accelerated phase and blast of chronic myeloid leukemia; Patients with relapsed AML; Allergy to any drug involved in the program; Pregnant, lactating women and patients of childbearing age who are unwilling to take contraceptive measures; The liver and kidney functions are obviously abnormal, exceeding the inclusion criteria; Structural heart disease, such as uncontrolled or symptomatic arrhythmia, congestive heart disease, heart failure or myocardial infarction within 6 months prior to screening, resulting in clinical symptoms or abnormal cardiac function; Suffering from other malignant tumors at the same time; except for the following cases: ①Have received treatment for the purpose of cure, and have no known active malignance for ≥5 years before enrollment; ② Adequately treated non-melanoma skin cancer or malignant lentigo with no signs of disease (even if less than 3 years before randomization); ③ Adequately treated carcinoma in situ with no signs of disease (even if less than 3 years before randomization); AIDS patients, syphilis patients, active type Hepatitis B (HBV-DNA detectable) patients, and Hepatitis C patients; Any concurrent medical condition or disease (such as active systemic infection) that may interfere with study procedures or results, or which, in the judgment of the investigator, poses a risk to participation in this study； Inability to understand or comply with the research protocol; Received major surgery within 4 weeks before randomization; Participate in other clinical investigators at the same time one month before enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenjie Liu, M.D
Phone
+8615895891160
Email
dreaming88516@sina.com
Facility Information:
Facility Name
The First Affiliated Hospital with Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenjie Liu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Venetoclax+HMA+Aclarubicin Versus Venetoclax+HMA in Treatment-Naive Elderly Patients With AML

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