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

NCT ID: NCT05841771

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-12-31

Brief 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 .

Detailed 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.

Conditions

Hypomethylating Agent; Venetoclax; Myeloid Malignancy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AZA-VEN maintenance

hypomethylating agents (azacytidine 32mg/m2 or decitabine 5mg/m2) for 5 days and venetoclax 400mg/d for 7 days, repeated every 28 days until up to 1-year posttransplant.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

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

Intervention Type: DRUG

azacytidine 32mg/m2 or decitabine 5mg/m2

Interventions

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.

Intervention Type: DRUG

Azacitidine or decitabine

azacytidine 32mg/m2 or decitabine 5mg/m2

Intervention Type: DRUG

Other Intervention Names

BCL-2 inhibitor; Hypomethylating Agent

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Liping Wan

Associate Director of Department of Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Liping Wan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Shanghai Jiao Tong University School of Medicine Affiliated Shanghai General Hospital

Locations

Shanghai Jiao Tong University School of Medicine Affilated Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xueying Ding, Ph.D.

Role: CONTACT

shiyicss@126.com

8621-36126060

Facility Contacts

Xueying Ding, Ph.D

Role: primary

shiyicss@126.com

86-21-36126060

Yanhong Zhu, M.S

Role: backup

sfph_edu2@163.com

86-21-63240090 ext. 6213

Other Identifiers

SHSYXY-AZA-VEN-202301

Identifier Type: -

Identifier Source: org_study_id