Hypomethylating Agent and Venetoclax After Allo-HSCT in Patients With High-risk Myeloid Malignancies.

Myeloid Malignancy Clinical Trial

Official title:

A Single Arm, Phase 2 Study Evaluating Safety and Efficacy of Maintenance Therapy With Hypomethylating Agent and Venetoclax After Allogeneic Stem Cell Transplantation in Patients With f High-risk Myeloid Malignancies.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05841771
• Other study ID #: SHSYXY-AZA-VEN-202301
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: Xueying Ding, Ph.D.
• Phone: 8621-36126060
• Email: shiyicss[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of the study is to evaluate the efficacy and safety of maintenance therapy with hypomethylating agent and Venetoclax to improve leukemia free survival for high-risk myeloid malignancies after allogeneic hematopoietic stem cell transplantation .

Description:

This is a prospective single-arm study. Patients with high-risk AML or MDS aged between 18-70 years old will enroll in the study. They will be given hypomethylating agents (azacytidine 32mg/m2 or decitabine 5mg/m2) for 5 days and venetoclax 400mg/d for 7 days after allogeneic hematopoietic stem cell transplantation. The maintenance therapy will start from 60th days posttransplant, repeated every 28 days until up to 1-year posttransplant. The 1-year leukemia-free survival rate，1-year cumulative recurrence rate, and 1-year overall survival will be analyzed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients with AML or MDS and have received allogeneic hematopoietic cell transplantation;

• Patients with AML must have one of the following high-risk factors: Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML; require more than 2 courses of induction chemotherapy to reach complete remission; Extramedullary myeloid malignancy;=CR2; Presence of measurable residual disease at the time of HSCT. *

• Patients with MDS must have one of the following high-risk factors: IPSS-R scores are high-risk or very high-risk; Presence of TP53 mutation; Presence of measurable residual disease at the time of HSCT. *

• CBC: ANC = 1.0 × 10e9/L, Hb = 80g/L, and PLT = 50 × 10e9/L;

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

• Presence of measurable residual disease at the time of HSCT is defined as the following: Blast percentage in bone marrow detected by flow cytometry =0.01%; Presence of fusion gene or mutated gene by qPCR.

Exclusion Criteria:

• Concurrent use of targeted drugs ;

• Resistant to Venetoclax before transplantation;

• Allergic to decitabine , Azacitidine or venetoclax;

• Active grade II or higher acute GVHD ;

• Active moderate or severe chronic GVHD ;

• Diseases recurrence (abnormal myeloid cells detected by flow cytometry >0.01%, presence of WT1 or other genes, or extramedullary malignancy ), percentage of donor cells in bone marrow <90% or graft rejection:

• CBC: ANC < 1.0 × 10e9/L, or PLT < 50 × 10e9/L;

• Severe organ dysfunction: Elevated Aspartate transaminase (AST) /alanine transaminase (ALT), or direct bilirubin >3 times upper limit of normal; Creatinine clearance (Ccr)<50mL/min or serum creatinine >1.5 times upper limit of normal, whether hemodialysis treatment is performed;

• Active uncontrolled systemic fungal, bacterial, or viral infection

• Pregnant or lactating women;

• Other severe complications and not suitable judged by researchers.

Related Conditions & MeSH terms

• Myeloid Malignancy
• Neoplasms
• Venetoclax

Intervention

Drug:
• Venetoclax
Participants will receive maintenance therapy with venetoclax and azacitidine or decitabine after allogeneic stem cell transplantation. Azacitidine will be administered once daily subcutaneously (32mg/m2/d) on days 1-5, and venetoclax will be administered once daily orally (400mg/day) on days 1-7. If the patient is refractory or allergic to azacitidine, they will receive decitabine. Decitabine will be administered intravenously (5mg/m2/d) on days 1-5. If the patient is treated with CYP450 inhibitors(such as posaconazole or voriconazole), the dose of venetoclax will reduce to 100 mg once daily on days 1-7. Maintenance therapy will start from the 60th to 120th days after allogeneic hematopoietic stem cell transplantation and repeat every 28 days for up to 10 cycles within the first year after transplantation.
• Azacitidine or decitabine
azacytidine 32mg/m2 or decitabine 5mg/m2

Locations

Country	Name	City	State
China	Shanghai Jiao Tong University School of Medicine Affilated Shanghai General Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Leukemia-free survival (LFS) time	Summary statistics for LFS time will be computed for all patients.	From the date of transplantation, assessed up to 1 year after transplantation.
Secondary	Cumulative incidence of relapse	Use the method of Gooley et al to estimate the cumulative incidence of relapse.	From the date of transplantation, assessed up to 1 year after transplantation.
Secondary	Overall survival	The method of Kaplan and Meier will be used to estimate the distribution of overall survival. Cox proportional hazards regression analysis will be used to model the association between overall survival and covariates of interest.	From the date of transplantation, assessed up to 1 year after transplantation.
Secondary	Incidence of toxicity of the regimen	Descriptive statistics will be used to summarize adverse events.	From the date of transplantation, assessed up to 1 year after transplantation.