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Clinical Study of Venetoclax Combined With CAG in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Ven+CAG
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 18 years ≤ age ≤ 75 years, male and female are not limited. According to bone marrow morphology and immunophenotype, it was diagnosed as acute myeloid leukemia ( WHO 2016 diagnostic criteria). Morphological recurrence after complete remission (CR) (leukemic cells in the peripheral blood of CR patients or more than 5% of the blasts in the bone marrow or new pathological hematopoiesis or extramedullary leukemic cell infiltration) or acute myeloid leukemia patients who did not achieved CR after 1 cycle of chemotherapy. The ECOG (Eastern Cancer Cooperation Group of the United States) PS score is 0-1. The expected survival time is ≥ 12 weeks. Female patients of childbearing age need to undergo pregnancy examination before receiving chemotherapy, and must agree to take effective contraceptive measures during treatment. Subjects volunteered to participate, fully informed consent, signed an informed consent, and good compliance. Exclusion Criteria: Other malignant hematological diseases that do not conform to the diagnosis of acute myeloid leukemia. Allergy to any drugs involved in the project. History of serious cardiovascular and cerebrovascular diseases: ① Congestive heart failure, unstable angina pectoris, myocardial infarction, stroke or poorly controlled arrhythmia with NYHA grade II or above occurred within 12 months before enrollment,LVEF (left ventricular ejection fraction)<50% by color Doppler ultrasound,Corrected QT interval (QTc)>480ms (calculated by Fridericia method, if the QTc is abnormal, it can be detected continuously for 3 times every 2 minutes, and the average value is taken),Hypertension difficult to control by drugs (systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg) (based on the average of ≥ 3 BP readings obtained from ≥ 2 measurements),Have had hypertensive crisis or hypertensive encephalopathy in the past. There are other obvious bleeding tendencies or evidence of major coagulation disorders: ①Hemoptysis of any reason occurred within 2 weeks before enrollment,② Thrombosis or embolism occurred within 6 months before enrollment,③ Anticoagulant therapy for therapeutic purposes (except low molecular weight heparin therapy) be used within 2 weeks before enrollment④ Antiplatelet therapy is required. Abnormal liver function: total bilirubin>3 mg/dL;Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 × Upper limit of normal value (ULN). Abnormal renal function: serum creatinine ≥ 1.5 × ULN, or the creatinine clearance rate (CrCl) calculated according to Cockroft-Gault formula is less than 60 mL/min (if the calculated CrCl is less than 60 mL/min, the researcher may ask to confirm the 24-hour CrCl, in this case, the subjects with 24-hour CrCl less than 60 mL/min should be excluded). Other serious diseases that may limit the patient's participation in this clinical trial (including but not limited to other malignant tumors, active infection, serious uncured wounds, active ulcers and untreated fractures, history of human immunodeficiency virus infection, and receiving allogeneic stem cells or solid organ transplantation). Cannot swallow pills, malabsorption syndrome or any condition that affects gastrointestinal absorption. Other clinical trials are being conducted. Unable to understand or cooperate to complete the research protocol. Pregnant and lactating patients Other situations that the researcher believes are not suitable for inclusion in the study.

Sites / Locations

  • Peking University People's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ven+CAG

Arm Description

Venetoclax plus CAG regimen

Outcomes

Primary Outcome Measures

CR/CRi rate
the rate of complete remission or complete remission with incomplete hematologic recovery
CR/CRi rate
the rate of complete remission or complete remission with incomplete hematologic recovery

Secondary Outcome Measures

MRD status
MRD-positive status was defined as FCM positivity in two consecutive BM samples at a 2-week interval, PCR positivity in two consecutive BM samples at a 2-week interval, or both FCM and PCR positivity in a single BM sample after the first-month post-HSCT. Positive FCM was defined as >0.01% of cells with a LAIPs phenotype in >1 BM samples after transplantation. The expressions of leukemia-associated genes were evaluated by TaqMan-based RT-PCR, including Wilms' tumor gene 1 (WT1) and genes which were determined in the diagnostic specimens.
MRD status
MRD-positive status was defined as FCM positivity in two consecutive BM samples at a 2-week interval, PCR positivity in two consecutive BM samples at a 2-week interval, or both FCM and PCR positivity in a single BM sample after the first-month post-HSCT. Positive FCM was defined as >0.01% of cells with a LAIPs phenotype in >1 BM samples after transplantation. The expressions of leukemia-associated genes were evaluated by TaqMan-based RT-PCR, including Wilms' tumor gene 1 (WT1) and genes which were determined in the diagnostic specimens.
objective remission rate(ORR)
The percentage of people in a study or treatment group who have a partial response or complete response to the treatment within a certain period of time.
objective remission rate(ORR)
The percentage of people in a study or treatment group who have a partial response or complete response to the treatment within a certain period of time.
Progression-free survival (PFS)
From date of Ven plus CAG therapy beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall survival
From date of Ven plus CAG therapy beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
The incidence of adverse events
According to Common Terminology Criteria for Adverse Events, CTCAE, V5.0, assessed up to 24 months

Full Information

First Posted
May 24, 2023
Last Updated
June 23, 2023
Sponsor
Peking University People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05918198
Brief Title
Clinical Study of Venetoclax Combined With CAG in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia
Official Title
Clinical Study of BCL-2 Inhibitor Venetoclax Combined With CAG in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 30, 2023 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University People's Hospital

4. Oversight

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

5. Study Description

Brief Summary
The goal of this clinical trial is to test the safety and efficacy of venetoclax plus CAG regimen in refractory/relapsed acute myeloid leukemia patients.
Detailed Description
The main questions it aims to answer are: Safety of Ven combined with CAG regimen in the treatment of relapsed/refractory AML patients Efficacy of Ven combined with CAG regimen in the treatment of relapsed/refractory AML patients Participants will receive therapy of venetoclax and CAG regimen (Ara-C, Acla and C C-GSF)

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 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ven+CAG
Arm Type
Experimental
Arm Description
Venetoclax plus CAG regimen
Intervention Type
Drug
Intervention Name(s)
Ven+CAG
Other Intervention Name(s)
Venetoclax plus CAG regimen
Intervention Description
100 mg on the first day, and then gradually increase to the target dose of 400 mg (100 mg d1, 200 mg d2, 400 mg d3) within 3 days; After that, the drug continued to be administered until the 14th day, 400 mg/day. When combined with CYP3A or P-gp inhibitors (mainly voriconazole in this study), adjust the venetoclax dose to 100 mg/day. Ara-C 10mg/m2, ih, q12h × 14d; Acla 20mg/d × 4d; G-CSF 5ug/kg × 14d (WBC > 30 × 10^9/L pause)
Primary Outcome Measure Information:
Title
CR/CRi rate
Description
the rate of complete remission or complete remission with incomplete hematologic recovery
Time Frame
2 to 3 weeks after the end of cycle 1 (each cycle is 14 days)
Title
CR/CRi rate
Description
the rate of complete remission or complete remission with incomplete hematologic recovery
Time Frame
2 to 3 weeks after the end of cycle 2 (each cycle is 14 days)
Secondary Outcome Measure Information:
Title
MRD status
Description
MRD-positive status was defined as FCM positivity in two consecutive BM samples at a 2-week interval, PCR positivity in two consecutive BM samples at a 2-week interval, or both FCM and PCR positivity in a single BM sample after the first-month post-HSCT. Positive FCM was defined as >0.01% of cells with a LAIPs phenotype in >1 BM samples after transplantation. The expressions of leukemia-associated genes were evaluated by TaqMan-based RT-PCR, including Wilms' tumor gene 1 (WT1) and genes which were determined in the diagnostic specimens.
Time Frame
2 to 3 weeks after the end of cycle 1 (each cycle is 14 days)
Title
MRD status
Description
MRD-positive status was defined as FCM positivity in two consecutive BM samples at a 2-week interval, PCR positivity in two consecutive BM samples at a 2-week interval, or both FCM and PCR positivity in a single BM sample after the first-month post-HSCT. Positive FCM was defined as >0.01% of cells with a LAIPs phenotype in >1 BM samples after transplantation. The expressions of leukemia-associated genes were evaluated by TaqMan-based RT-PCR, including Wilms' tumor gene 1 (WT1) and genes which were determined in the diagnostic specimens.
Time Frame
2 to 3 weeks after the end of cycle 2 (each cycle is 14 days)
Title
objective remission rate(ORR)
Description
The percentage of people in a study or treatment group who have a partial response or complete response to the treatment within a certain period of time.
Time Frame
2 to 3 weeks after the end of cycle 1 (each cycle is 14 days)
Title
objective remission rate(ORR)
Description
The percentage of people in a study or treatment group who have a partial response or complete response to the treatment within a certain period of time.
Time Frame
2 to 3 weeks after the end of cycle 2 (each cycle is 14 days)
Title
Progression-free survival (PFS)
Description
From date of Ven plus CAG therapy beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Time Frame
Throughout the whole research process, assessed up to 24 months
Title
Overall survival
Description
From date of Ven plus CAG therapy beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Time Frame
Throughout the whole research process, assessed up to 24 months
Title
The incidence of adverse events
Description
According to Common Terminology Criteria for Adverse Events, CTCAE, V5.0, assessed up to 24 months
Time Frame
Throughout the whole research process, assessed up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years ≤ age ≤ 75 years, male and female are not limited. According to bone marrow morphology and immunophenotype, it was diagnosed as acute myeloid leukemia ( WHO 2016 diagnostic criteria). Morphological recurrence after complete remission (CR) (leukemic cells in the peripheral blood of CR patients or more than 5% of the blasts in the bone marrow or new pathological hematopoiesis or extramedullary leukemic cell infiltration) or acute myeloid leukemia patients who did not achieved CR after 1 cycle of chemotherapy. The ECOG (Eastern Cancer Cooperation Group of the United States) PS score is 0-1. The expected survival time is ≥ 12 weeks. Female patients of childbearing age need to undergo pregnancy examination before receiving chemotherapy, and must agree to take effective contraceptive measures during treatment. Subjects volunteered to participate, fully informed consent, signed an informed consent, and good compliance. Exclusion Criteria: Other malignant hematological diseases that do not conform to the diagnosis of acute myeloid leukemia. Allergy to any drugs involved in the project. History of serious cardiovascular and cerebrovascular diseases: ① Congestive heart failure, unstable angina pectoris, myocardial infarction, stroke or poorly controlled arrhythmia with NYHA grade II or above occurred within 12 months before enrollment,LVEF (left ventricular ejection fraction)<50% by color Doppler ultrasound,Corrected QT interval (QTc)>480ms (calculated by Fridericia method, if the QTc is abnormal, it can be detected continuously for 3 times every 2 minutes, and the average value is taken),Hypertension difficult to control by drugs (systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg) (based on the average of ≥ 3 BP readings obtained from ≥ 2 measurements),Have had hypertensive crisis or hypertensive encephalopathy in the past. There are other obvious bleeding tendencies or evidence of major coagulation disorders: ①Hemoptysis of any reason occurred within 2 weeks before enrollment,② Thrombosis or embolism occurred within 6 months before enrollment,③ Anticoagulant therapy for therapeutic purposes (except low molecular weight heparin therapy) be used within 2 weeks before enrollment④ Antiplatelet therapy is required. Abnormal liver function: total bilirubin>3 mg/dL;Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 × Upper limit of normal value (ULN). Abnormal renal function: serum creatinine ≥ 1.5 × ULN, or the creatinine clearance rate (CrCl) calculated according to Cockroft-Gault formula is less than 60 mL/min (if the calculated CrCl is less than 60 mL/min, the researcher may ask to confirm the 24-hour CrCl, in this case, the subjects with 24-hour CrCl less than 60 mL/min should be excluded). Other serious diseases that may limit the patient's participation in this clinical trial (including but not limited to other malignant tumors, active infection, serious uncured wounds, active ulcers and untreated fractures, history of human immunodeficiency virus infection, and receiving allogeneic stem cells or solid organ transplantation). Cannot swallow pills, malabsorption syndrome or any condition that affects gastrointestinal absorption. Other clinical trials are being conducted. Unable to understand or cooperate to complete the research protocol. Pregnant and lactating patients Other situations that the researcher believes are not suitable for inclusion in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wen-Jing Yu, M.D.
Phone
18813187365
Email
yuwenjing789@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wen-Jing Yu, M.D.
Organizational Affiliation
Peking University People's Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wen-Jing Yu
Phone
18813187365
Email
yuwenjing789@126.com

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Undecided

Learn more about this trial

Clinical Study of Venetoclax Combined With CAG in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia

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