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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Malignancy; Stem Cell Transplant Complications
• Intervention / Treatment: Drug: Azacitidine in Combination With Venetoclax

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 Type: Interventional
• Enrollment (Anticipated): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse-free survival	relapse-free survival	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	overall survival	2 year
graft-versus-host disease -free relapse-free survival	graft-versus-host disease -free relapse-free survival	2 year
cumulative incidence of aGVHD	cumulative incidence of aGVHD	100 days
cumulative incidence of cGVHD	cumulative incidence of cGVHD	2 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2021
• Primary Completion (Anticipated): March 19, 2024
• Study Completion (Anticipated): March 19, 2026

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 19, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Venetoclax; Azacitidine; Relapse; Allogeneic Hematopoietic stem cell transplantation; Micro residual disease
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: ZJU-HSCT-AZA02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No