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

Sponsor

First Affiliated Hospital of Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04809181

Collaborator

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

Enrollment

Location

Arm

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancy Stem Cell Transplant Complications	Drug: Azacitidine in Combination With Venetoclax	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

95 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Mar 19, 2021

Anticipated Primary Completion Date :

Mar 19, 2024

Anticipated Study Completion Date :

Mar 19, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MRD positive AML/MDS patients after allogeneic hematopoietic stem cell transplantation MRD positive AML/MDS patients after allogeneic hematopoietic stem cell transplantation	Drug: Azacitidine in Combination With Venetoclax Azacitidine in combination with venetoclax

Arm

Intervention/Treatment

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

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

Drug: Azacitidine in Combination With Venetoclax

Azacitidine in combination with venetoclax

Outcome Measures

Primary Outcome Measures

relapse-free survival [2 year]
relapse-free survival

Secondary Outcome Measures

overall survival [2 year]
overall survival
graft-versus-host disease -free relapse-free survival [2 year]
graft-versus-host disease -free relapse-free survival
cumulative incidence of aGVHD [100 days]
cumulative incidence of aGVHD
cumulative incidence of cGVHD [2 year]
cumulative incidence of cGVHD

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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.