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VCA Regimen Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Primary Purpose

Leukemia, Myeloid, Acute, AML Stage, Adult

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Venetoclax Combining Chidamide and Azacitidine (VCA) regimen followed by dicitabine combined with liposome mitoxantrone, cytarabine, and G-CSF (D-MAG) regimen
Sponsored by
The First Affiliated Hospital of Xiamen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring newly diagnosed acute myeloid leukemia, liposome mitoxantrone, sequential treatment

Eligibility Criteria

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

Inclusion Criteria: 1) Histologically confirmed acute myeloid leukemia (non-M3). Treatment-na?ve and unable to receive standard cytarabine and anthracycline induction regimens due to age or comorbidities or patient preference. 2) Age ≥ 60 years old, male or female, with an expected survival more than 3 months. 3) Estimated creatinine clearance ≥ 30 mL/min. 4) AST and ALT ≤ 3.0 x ULN (unless leukemic organ involvement). Bilirubin ≤ 1.5 x ULN (unless considered due to leukemic organ involvement). 5) ECOG ≤ 2. 6) Able to understand and voluntarily provide informed consent. Exclusion Criteria: 1)Acute promyelocytic leukemia (APL) and low risk cytogenetics such as t(8;21), inv(16) or t(16;16). 2) Active central nervous system leukemia. 3) History of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR- ABL1 translocation. 4) HIV positive patients and/or HBV or HCV active infection (documented by HBV-DNA and HCV-RNA positive test) 5) Patients suffering from chronic respiratory diseases that require continuous oxygen inhalation, or a history of obvious renal, nervous system, psychiatric, endocrine, metabolic, immune, liver, and cardiovascular diseases 6) Patients suffering from malabsorption syndrome or other conditions that exclude enteral route of administration. 7) Patients has clinically significant QTc prolongation (>450 ms in men; >470 ms in women), ventricular tachycardia and atrial fibrillation, second-degree heart block, myocardial infarction within the year prior to enrollment, and congestive heart failure;and patients with coronary heart disease with clinical symptoms requiring drug treatment. 8) Active, uncontrolled severe infection. 9) History of other malignancies within 2 years, except for the following: Adequately treated cervix or breast cancer in situ; Basal cell cancer or local squamous cell carcinoma of the skin; 10) White blood cell count > 25 × 10^9/L. (Hydroxyurea or leukapheresis may meet this criterion.) 11) Mental disorders that hinder research participation 12) Participants have received the following treatments: hypomethylating agents, veneclax and/or chemotherapy for myelodysplastic syndrome (MDS), solid organ transplantation. 13) Any other circumstances that the investigator believes that the patient is not suitable to participate in this trial

Sites / Locations

  • Bing Xu

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

treatment arm

Arm Description

2 cycles of VCA regimens followed by 2 cycles of D-MAG regimens, and then repeat the above four courses of treatment once

Outcomes

Primary Outcome Measures

Complete remission (CR) rate
CR was <5% marrow blasts by morphology

Secondary Outcome Measures

1 year leukemia free survival (LFS)
Leukemia-free survival (LFS) is defined as survival without evidence of relapse from treatment initiation
1 year overall survival (OS)
Overall survival(OS)is defined as the time from treatment initiation to death from any cause.
Adverse events
Adverse event is defined as any untoward medical occurrence associated with treatment
objective response rate (ORR)
ORR is defined as CR, CRi and PR. Partial remission (PR) is defined as a decrease of at least 50% in the percentage of blasts to 5 to 25% in the bone marrow aspirate and the normalization of blood counts.

Full Information

First Posted
October 29, 2022
Last Updated
October 29, 2022
Sponsor
The First Affiliated Hospital of Xiamen University
Collaborators
Chipscreen Biosciences, Ltd., CSPC Pharmaceutical Group Limited, Fujian Provincial Hospital, Fujian Cancer Hospital, Zhangzhou manicipal hospital of Fujian Province, Jieyang People's Hospital, Huizhou Municipal Central Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05603884
Brief Title
VCA Regimen Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Official Title
Venetoclax Combining Chidamide and Azacitidine (VCA) Regimen Followed by Dicitabine Combined With Liposome Mitoxantrone, Cytarabine, and G-CSF (D-MAG) Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) : A Multicenter, Prospective, Single Arm Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2022 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Xiamen University
Collaborators
Chipscreen Biosciences, Ltd., CSPC Pharmaceutical Group Limited, Fujian Provincial Hospital, Fujian Cancer Hospital, Zhangzhou manicipal hospital of Fujian Province, Jieyang People's Hospital, Huizhou Municipal Central 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
The purpose of this study is to evaluate the safety and efficacy of Venetoclax Combining Chidamide and Azacitidine (VCA) Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Detailed Description
Elderly Patients with AML have inferior outcomes due to poor physical condition, and intolerant to conventional chemotherapy. The regimen of Venetoclax and Azacitidine has been widely used in these patients and has proved to achieve higher CR rate than low intensity therapy. However, the median duration of response (DOR) of this regimen is about one year. Chidamide is a histone deacetylase (HDAC) inhibitor and preclinical data showed adding low-dose Chidamide to venetoclax could significantly promoted apoptosis of leukemia cell lines. The Venetoclax Combining Chidamide and Azacitidine (VCA) regimen was applied to one 62-year-old male patient with AML who achieved CR. Meanwhile, Liposome mitoxantrone has better safety and tolerance than mitoxantrone in elderly patients. Thus, this study is intended to use 2 cycles of VCA regimens followed by 2 cycles of D-MAG regimens, and then repeat the above four courses of treatment once to improve the median event free survival of elderly AML patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute, AML Stage, Adult
Keywords
newly diagnosed acute myeloid leukemia, liposome mitoxantrone, sequential treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
treatment arm
Arm Type
Experimental
Arm Description
2 cycles of VCA regimens followed by 2 cycles of D-MAG regimens, and then repeat the above four courses of treatment once
Intervention Type
Drug
Intervention Name(s)
Venetoclax Combining Chidamide and Azacitidine (VCA) regimen followed by dicitabine combined with liposome mitoxantrone, cytarabine, and G-CSF (D-MAG) regimen
Intervention Description
venetoclax combining chidamide and azacitidine (VCA) 28 days per cycle × 2 cycles; 1) chidamide 30mg biw × 2weeks;2) venetoclax 200mg/d × 2 weeks 3) azacitidine 100mg/d d1-7 dicitabine combined with liposome mitoxantrone, cytarabine, and G-CSF (D-MAG) regimen 28 days per cycle ×2 cycles; 1)dicitabine 25mg d1-3,2)liposome mitoxantrone 20mg d4,3)cytarabine 10mg/m2 Q12h d1-7 4)G-CSF 300ug d-1 until WBC > 20×109/L
Primary Outcome Measure Information:
Title
Complete remission (CR) rate
Description
CR was <5% marrow blasts by morphology
Time Frame
6 months
Secondary Outcome Measure Information:
Title
1 year leukemia free survival (LFS)
Description
Leukemia-free survival (LFS) is defined as survival without evidence of relapse from treatment initiation
Time Frame
1 year from treatment initiation
Title
1 year overall survival (OS)
Description
Overall survival(OS)is defined as the time from treatment initiation to death from any cause.
Time Frame
1 year from treatment initiation
Title
Adverse events
Description
Adverse event is defined as any untoward medical occurrence associated with treatment
Time Frame
6 months
Title
objective response rate (ORR)
Description
ORR is defined as CR, CRi and PR. Partial remission (PR) is defined as a decrease of at least 50% in the percentage of blasts to 5 to 25% in the bone marrow aspirate and the normalization of blood counts.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1) Histologically confirmed acute myeloid leukemia (non-M3). Treatment-na?ve and unable to receive standard cytarabine and anthracycline induction regimens due to age or comorbidities or patient preference. 2) Age ≥ 60 years old, male or female, with an expected survival more than 3 months. 3) Estimated creatinine clearance ≥ 30 mL/min. 4) AST and ALT ≤ 3.0 x ULN (unless leukemic organ involvement). Bilirubin ≤ 1.5 x ULN (unless considered due to leukemic organ involvement). 5) ECOG ≤ 2. 6) Able to understand and voluntarily provide informed consent. Exclusion Criteria: 1)Acute promyelocytic leukemia (APL) and low risk cytogenetics such as t(8;21), inv(16) or t(16;16). 2) Active central nervous system leukemia. 3) History of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR- ABL1 translocation. 4) HIV positive patients and/or HBV or HCV active infection (documented by HBV-DNA and HCV-RNA positive test) 5) Patients suffering from chronic respiratory diseases that require continuous oxygen inhalation, or a history of obvious renal, nervous system, psychiatric, endocrine, metabolic, immune, liver, and cardiovascular diseases 6) Patients suffering from malabsorption syndrome or other conditions that exclude enteral route of administration. 7) Patients has clinically significant QTc prolongation (>450 ms in men; >470 ms in women), ventricular tachycardia and atrial fibrillation, second-degree heart block, myocardial infarction within the year prior to enrollment, and congestive heart failure;and patients with coronary heart disease with clinical symptoms requiring drug treatment. 8) Active, uncontrolled severe infection. 9) History of other malignancies within 2 years, except for the following: Adequately treated cervix or breast cancer in situ; Basal cell cancer or local squamous cell carcinoma of the skin; 10) White blood cell count > 25 × 10^9/L. (Hydroxyurea or leukapheresis may meet this criterion.) 11) Mental disorders that hinder research participation 12) Participants have received the following treatments: hypomethylating agents, veneclax and/or chemotherapy for myelodysplastic syndrome (MDS), solid organ transplantation. 13) Any other circumstances that the investigator believes that the patient is not suitable to participate in this trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bing Xu, M.D.
Phone
+865922137255
Email
xubingzhangjian@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bing Xu, M.D.
Organizational Affiliation
The First Affiliated Hospital of Xiamen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bing Xu
City
Xiamen
State/Province
Fujian
ZIP/Postal Code
361003
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

VCA Regimen Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

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