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Azacitidine in Combination With Venetoclax Treatment for MRD Positive Post Allo-HSCT AML/MDS Patients

Primary Purpose

Hematologic Malignancy, Stem Cell Transplant Complications

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Azacitidine in Combination With Venetoclax

About this trial

This is an interventional prevention trial for Hematologic Malignancy focused on measuring Allogeneic Hematopoietic stem cell transplantation, Micro residual disease, Azacitidine, Venetoclax, Relapse

Eligibility Criteria

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

Inclusion Criteria:

Patients between 18 years old and 65 years old.
Patients with AML or MDS diagnosed according to WHO diagnostic criteria.
Patients who received allogeneic hematopoietic stem cell transplantation and achieved complete remission.
MRD was positive after transplantation, MFC > 0.1% and / or fusion gene and gene mutation (WT1 > 0.6%, AML1-ETO > 0.4%, others >1%).
ECOG body status score 0-2.
Patients with expected survival time >=3 months.
Good organ function level: ANC (neutrophil absolute value >=1.0x10^9/L; PLT >=30x10^9/L; HB >=80g/L; Tibil <=1.5 ULN; ALT / AST <=2.5 ULN; bun / Cr <=1.5 ULN; LVEF >=50%).
Patients who have received any anti-tumor treatment (including radiotherapy, chemotherapy, surgery or molecular targeted treatment) for more than 4 weeks from the end of the previous treatment.
Patients with no GVHD and no previous history of 3 or more degrees of aGVHD. 10. Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing.

Exclusion Criteria:

Patients with severe cardiac insufficiency and EF lower than 60%; or patients with severe arrhythmia who could not tolerate super pretreatment.
Patients with activity of aGVHD or extensive cGVHD.
Patients with BCR/ABL positive.
Patients who were previously known to be resistant to azacytidine or dessicabine or venetoclax.
In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate the super pretreatment scheme.
Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of super pretreatment.
In patients with severe renal insufficiency, the renal function index (CR) is more than 2 times of the upper limit of the normal value (ULN), or the 24-hour creatinine clearance rate (CR) is less than 50ml / min, the researchers evaluated that they could not tolerate the super pretreatment scheme.
In patients with severe active infection, the researchers evaluated that they could not tolerate the pretreatment.
Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study.
Patients with hematological recurrence (bone marrow smear: proportion of primordial cells >=5%) or any extramedullary recurrence.
Other reasons why the researchers could not be selected.

Sites / Locations

The first Affiliated Hospital of Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MRD positive AML/MDS patients after allogeneic hematopoietic stem cell transplantation

Arm Description

MRD positive AML/MDS patients after allogeneic hematopoietic stem cell transplantation

Outcomes

Primary Outcome Measures

relapse-free survival

Secondary Outcome Measures

overall survival

graft-versus-host disease -free relapse-free survival

cumulative incidence of aGVHD

cumulative incidence of cGVHD

Full Information

NCT ID

NCT04809181

First Posted

March 19, 2021

Last Updated

February 19, 2023

Sponsor

First Affiliated Hospital of Zhejiang University

Collaborators

Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial People's Hospital, The First Affiliated Hospital of Zhejiang Chinese Medical University, Sir Run Run Shaw Hospital, First Affiliated Hospital of Wenzhou Medical University, Ningbo No. 1 Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Jinhua Central Hospital, Taizhou Hospital, Union hospital of Fujian Medical University, Xiangya Hospital of Central South University

1. Study Identification

Unique Protocol Identification Number

NCT04809181

Brief Title

Azacitidine in Combination With Venetoclax Treatment for MRD Positive Post Allo-HSCT AML/MDS Patients

Official Title

Azacitidine in Combination With Venetoclax Treatment for Prevention of Relapse in MRD Positive Post Allogeneic Hematopoietic Stem Cell Transplantation Acute Myelogenous Leukemia/ Myelodysplastic Syndrome Patients

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 19, 2021 (Actual)

Primary Completion Date

March 19, 2024 (Anticipated)

Study Completion Date

March 19, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

First Affiliated Hospital of Zhejiang University

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

In patients with MRD-positive patients after AML/MDS allogeneic hematopoietic stem cell transplantation, azacytidine combined with venetoclax may be effective in eliminating micro residual diseases, reducing the risk of relapse, and ultimately improving long-term survival.The primary purpose of this study was to explore an effective protocol to reduce the risk of relapse in patients with MRD positive after allogeneic hematopoietic stem cell transplantation for AML/MDS.

Detailed Description

The technology of Allogeneic Hematopoietic stem cell transplantation (allo-HSCT) has been continuously improved, relpase is still the leading cause of death after allo-HSCT. Monitoring of micro residual disease (MRD) after allogeneic HSCT provides a risk stratification of relpase risk in patients after transplantation.There is an urgent need to find an effective intervention plan for patients with MRD positive after transplantation, in order to reduce the risk of relapse after transplantation and improve long-term survival.The combination of demethylated drugs with venetoclax has shown promising results in clinical trials in AML patients who cannot tolerate induction chemotherapy.In patients with MRD-positive patients after AML/MDS allo-HSCT, azacytidine combined with venetoclax may be effective in eliminating small residual diseases, reducing the risk of relapse, and ultimately improving long-term survival.The primary purpose of this study was to explore an effective protocol to reduce the risk of relapse in patients with MRD positive after allo-HSCT for AML/MDS.

6. Conditions and Keywords

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

Hematologic Malignancy, Stem Cell Transplant Complications

Keywords

Allogeneic Hematopoietic stem cell transplantation, Micro residual disease, Azacitidine, Venetoclax, Relapse

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

95 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

MRD positive AML/MDS patients after allogeneic hematopoietic stem cell transplantation

Arm Type

Experimental

Arm Description

MRD positive AML/MDS patients after allogeneic hematopoietic stem cell transplantation

Intervention Type

Drug

Intervention Name(s)

Azacitidine in Combination With Venetoclax

Intervention Description

Azacitidine in combination with venetoclax

Primary Outcome Measure Information:

Title

relapse-free survival

Description

relapse-free survival

Time Frame

2 year

Secondary Outcome Measure Information:

Title

overall survival

Description

overall survival

Time Frame

2 year

Title

graft-versus-host disease -free relapse-free survival

Description

graft-versus-host disease -free relapse-free survival

Time Frame

2 year

Title

cumulative incidence of aGVHD

Description

cumulative incidence of aGVHD

Time Frame

100 days

Title

cumulative incidence of cGVHD

Description

cumulative incidence of cGVHD

Time Frame

2 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients between 18 years old and 65 years old. Patients with AML or MDS diagnosed according to WHO diagnostic criteria. Patients who received allogeneic hematopoietic stem cell transplantation and achieved complete remission. MRD was positive after transplantation, MFC > 0.1% and / or fusion gene and gene mutation (WT1 > 0.6%, AML1-ETO > 0.4%, others >1%). ECOG body status score 0-2. Patients with expected survival time >=3 months. Good organ function level: ANC (neutrophil absolute value >=1.0x10^9/L; PLT >=30x10^9/L; HB >=80g/L; Tibil <=1.5 ULN; ALT / AST <=2.5 ULN; bun / Cr <=1.5 ULN; LVEF >=50%). Patients who have received any anti-tumor treatment (including radiotherapy, chemotherapy, surgery or molecular targeted treatment) for more than 4 weeks from the end of the previous treatment. Patients with no GVHD and no previous history of 3 or more degrees of aGVHD. 10. Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing. Exclusion Criteria: Patients with severe cardiac insufficiency and EF lower than 60%; or patients with severe arrhythmia who could not tolerate super pretreatment. Patients with activity of aGVHD or extensive cGVHD. Patients with BCR/ABL positive. Patients who were previously known to be resistant to azacytidine or dessicabine or venetoclax. In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate the super pretreatment scheme. Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of super pretreatment. In patients with severe renal insufficiency, the renal function index (CR) is more than 2 times of the upper limit of the normal value (ULN), or the 24-hour creatinine clearance rate (CR) is less than 50ml / min, the researchers evaluated that they could not tolerate the super pretreatment scheme. In patients with severe active infection, the researchers evaluated that they could not tolerate the pretreatment. Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study. Patients with hematological recurrence (bone marrow smear: proportion of primordial cells >=5%) or any extramedullary recurrence. Other reasons why the researchers could not be selected.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yi Luo, M.D.

Phone

+86057187233801

luoyijr@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Yibo Wu, M.D.

Phone

+8619858876273

wuyibo7@126.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yi Luo, M.D.

Organizational Affiliation

First Affilaated Hospital of Medical School of Zhejiang University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The first Affiliated Hospital of Zhejiang University

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yi Luo, M.D.

Phone

+86057187233801

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Azacitidine in Combination With Venetoclax Treatment for MRD Positive Post Allo-HSCT AML/MDS Patients

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