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Venetoclax+Azacytidine+Modified BUCY Conditioning Regimen for Acute Myeloid Leukemia and Myelodysplastic Syndromes Undergoing Allo-HSCT

Primary Purpose

Allogeneic Hematopoietic Stem Cell Transplantation, Acute Myeloid Leukemia, Myelodysplastic Syndrome

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
VEN+AZA+Modified BUCY
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 Allogeneic Hematopoietic Stem Cell Transplantation focused on measuring venetoclax, azacytidine, hematopoietic stem cell transplantation, acute myeloid leukemia, myelodysplastic syndrome

Eligibility Criteria

8 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 8 to 65 years; Diseases must be MDS and AML; high-risk MDS: int-2 risk, high risk by the IPSS; IPSS-R int-risk (> 3.5 points), high risk, very high risk; high risk,very high risk by the WPSS; high-risk or relapsed/refractory AML: (1) age≥60 years; (2) High white blood cell count at first diagnosis (WBC≥100*10^9/L); (3) secondary AML (previous history of MDS, myeloproliferative disease, or treatment-related AML, etc.); (4) Complicated with extramedullary leukemia, such as central nervous system leukemia, granulocytic sarcoma, hepatosenomegaly; (5)high risk factors and relapsed/refractory AML(reference 2022-AML-ELN guideline)(6)not in remission or ≥CR2 before transplantation; Must need a bone marrow transplant; Must have the ability to observe the efficacy and events; Patient must have ability to understand and willingness to provide written informed consent prior to participation in the study and any related procedures being performed. Exclusion Criteria: Age <8 or >65 years; Uncontrolled bacterial, viral, fungal, or other infection before conditioning regimen; Pregnant or lactating females; Current participation in another clinical trial; Contra-indication to one of the drug of the regimen; Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo the agents included in the conditioning regimen.

Sites / Locations

  • The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

VEN+AZA+Modified BUCY

Arm Description

Outcomes

Primary Outcome Measures

disease-free survival (DFS)
It is measured from the time from randomization to the first of relapse or death.
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.

Secondary Outcome Measures

veno-occlusive disease (VOD)
incidence of veno-occlusive disease (VOD) events (refer to modified Seattle Criteria of VOD)
graft-versus-host disease (GvHD)
incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD) (aGvHD refer to Glucksberg Criteria and cGvHD refer to the National Institutes of Health Consensus)
transplant related mortality (TRM)
cumulative incidence of transplant related mortality
Regimen related toxicity
Number of participants with conditioning regimen related toxicity

Full Information

First Posted
February 27, 2023
Last Updated
April 10, 2023
Sponsor
The First Affiliated Hospital of Soochow University
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1. Study Identification

Unique Protocol Identification Number
NCT05823714
Brief Title
Venetoclax+Azacytidine+Modified BUCY Conditioning Regimen for Acute Myeloid Leukemia and Myelodysplastic Syndromes Undergoing Allo-HSCT
Official Title
Venetoclax + Azacytidine Followed by Modified BUCY Conditioning Regimen for High-risk Myelodysplastic Syndromes (MDS) and High-risk or Relapsed/Refractory Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 20, 2022 (Actual)
Primary Completion Date
January 20, 2025 (Anticipated)
Study Completion Date
January 20, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University

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 purpose of this prospective, open-label, single-center study is to evaluate the efficacy and safety of VEN-AZA (venetoclax and azacytidine) followed by modified BUCY (busulfan and cyclophosphamide) as conditioning regimen for high-risk myelodysplastic syndrome (MDS) and high-risk or relapsed/refractory acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Detailed Description
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only potentially curative therapy for patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, relapse remains a leading cause for treatment failure after hematopoietic cell transplantation (HCT) in patients, optimization of conditioning regimen can improve prognosis and decrease relapse. Abnormal gene methylation is common in AML and MDS patients. Azacytidine is a DNA methylation transferase inhibitor that can re-express tumor suppressor genes in leukemia cells. Venetoclax is a selective BCL-2 inhibitor, which has antitumor activity against a variety of hematological malignancies. The combination of the two drugs show a synergistic anti-tumor effect. The objective of this study is to evaluate the safety and efficacy of VEN-AZA regimen followed by Allo-HSCT in the treatment of high-risk MDS and high-risk or relapsed/refractory AML.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allogeneic Hematopoietic Stem Cell Transplantation, Acute Myeloid Leukemia, Myelodysplastic Syndrome
Keywords
venetoclax, azacytidine, hematopoietic stem cell transplantation, acute myeloid leukemia, myelodysplastic syndrome

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
VEN+AZA+Modified BUCY
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
VEN+AZA+Modified BUCY
Intervention Description
Venetoclax: 200mg/day*7days(It should be combined with triazole antifungal drugs). Azacytidine: 75mg/ m²/day*7days.
Primary Outcome Measure Information:
Title
disease-free survival (DFS)
Description
It is measured from the time from randomization to the first of relapse or death.
Time Frame
3 years after transplantation
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
3 years after transplantation
Secondary Outcome Measure Information:
Title
veno-occlusive disease (VOD)
Description
incidence of veno-occlusive disease (VOD) events (refer to modified Seattle Criteria of VOD)
Time Frame
3 years after transplantation
Title
graft-versus-host disease (GvHD)
Description
incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD) (aGvHD refer to Glucksberg Criteria and cGvHD refer to the National Institutes of Health Consensus)
Time Frame
3 years after transplantation
Title
transplant related mortality (TRM)
Description
cumulative incidence of transplant related mortality
Time Frame
3 years after transplantation
Title
Regimen related toxicity
Description
Number of participants with conditioning regimen related toxicity
Time Frame
3 years after transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 8 to 65 years; Diseases must be MDS and AML; high-risk MDS: int-2 risk, high risk by the IPSS; IPSS-R int-risk (> 3.5 points), high risk, very high risk; high risk,very high risk by the WPSS; high-risk or relapsed/refractory AML: (1) age≥60 years; (2) High white blood cell count at first diagnosis (WBC≥100*10^9/L); (3) secondary AML (previous history of MDS, myeloproliferative disease, or treatment-related AML, etc.); (4) Complicated with extramedullary leukemia, such as central nervous system leukemia, granulocytic sarcoma, hepatosenomegaly; (5)high risk factors and relapsed/refractory AML(reference 2022-AML-ELN guideline)(6)not in remission or ≥CR2 before transplantation; Must need a bone marrow transplant; Must have the ability to observe the efficacy and events; Patient must have ability to understand and willingness to provide written informed consent prior to participation in the study and any related procedures being performed. Exclusion Criteria: Age <8 or >65 years; Uncontrolled bacterial, viral, fungal, or other infection before conditioning regimen; Pregnant or lactating females; Current participation in another clinical trial; Contra-indication to one of the drug of the regimen; Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo the agents included in the conditioning regimen.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaowen Tang, MD
Phone
+86-512-67781851
Email
xwtang1020@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Depei Wu, MD
Phone
+86-512-67781851
Email
wudepei@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Depei Wu Wu, MD
Organizational Affiliation
The First Affiliated Hospital of Soochow University
Official's Role
Study Chair
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaowen Tang, PhD
Phone
67781525
Email
xwtang1020@163.com

12. IPD Sharing Statement

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Venetoclax+Azacytidine+Modified BUCY Conditioning Regimen for Acute Myeloid Leukemia and Myelodysplastic Syndromes Undergoing Allo-HSCT

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