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

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 2

Conditions: Myeloid Malignancy; Venetoclax; Hypomethylating Agent

Treatments: Drug: Azacitidine or decitabine; Drug: Venetoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT05841771

SHSYXY-AZA-VEN-202301

Details and patient eligibility

About

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 .

Full 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.

Enrollment: 78 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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78 participants in 1 patient group

AZA-VEN maintenance

Experimental group

Description:

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.

Treatment:

Drug: Venetoclax

Drug: Azacitidine or decitabine