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

Hematologic Malignancy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04809181
• Other study ID #: ZJU-HSCT-AZA02
• Status: Recruiting
• Phase: Phase 2
• Start date: March 19, 2021
• Est. completion date: March 19, 2026

Study information

• Verified date: February 2023
• Source: First Affiliated Hospital of Zhejiang University
• Contact: Yi Luo, M.D.
• Phone: +86057187233801
• Email: luoyijr[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 95
• Est. completion date: March 19, 2026
• Est. primary completion date: March 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Patients between 18 years old and 65 years old.

2. Patients with AML or MDS diagnosed according to WHO diagnostic criteria.

3. Patients who received allogeneic hematopoietic stem cell transplantation and achieved complete remission.

4. MRD was positive after transplantation, MFC > 0.1% and / or fusion gene and gene mutation (WT1 > 0.6%, AML1-ETO > 0.4%, others >1%).

5. ECOG body status score 0-2.

6. Patients with expected survival time >=3 months.

7. 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%).

8. 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.

9. 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:

1. Patients with severe cardiac insufficiency and EF lower than 60%; or patients with severe arrhythmia who could not tolerate super pretreatment.

2. Patients with activity of aGVHD or extensive cGVHD.

3. Patients with BCR/ABL positive.

4. Patients who were previously known to be resistant to azacytidine or dessicabine or venetoclax.

5. 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.

6. Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of super pretreatment.

7. 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.

8. In patients with severe active infection, the researchers evaluated that they could not tolerate the pretreatment.

9. Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study.

10. Patients with hematological recurrence (bone marrow smear: proportion of primordial cells >=5%) or any extramedullary recurrence.

11. Other reasons why the researchers could not be selected.

Related Conditions & MeSH terms

• Hematologic Malignancy
• Hematologic Neoplasms
• Stem Cell Transplant Complications

Intervention

Drug:
• Azacitidine in Combination With Venetoclax
Azacitidine in combination with venetoclax

Locations

Country	Name	City	State
China	The first Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang

Sponsors (12)

Lead Sponsor

Collaborator

First Affiliated Hospital of Zhejiang University

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	relapse-free survival	relapse-free survival	2 year
Secondary	overall survival	overall survival	2 year
Secondary	graft-versus-host disease -free relapse-free survival	graft-versus-host disease -free relapse-free survival	2 year
Secondary	cumulative incidence of aGVHD	cumulative incidence of aGVHD	100 days
Secondary	cumulative incidence of cGVHD	cumulative incidence of cGVHD	2 year