Venetoclax+Azacytidine+Modified BUCY Conditioning Regimen for Acute Myeloid Leukemia and Myelodysplastic Syndromes Undergoing Allo-HSCT

NCT ID: NCT05823714

Last Updated: 2023-04-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-20
• Study Completion Date: 2026-01-20

Brief Summary

The purpose of this prospective, open-label, single-center study is to evaluate the efficacy and safety of VEN-AZA (venetoclax and azacytidine) followed by modified BUCY (busulfan and cyclophosphamide) as conditioning regimen for high-risk myelodysplastic syndrome (MDS) and high-risk or relapsed/refractory acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Detailed Description

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only potentially curative therapy for patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, relapse remains a leading cause for treatment failure after hematopoietic cell transplantation (HCT) in patients, optimization of conditioning regimen can improve prognosis and decrease relapse. Abnormal gene methylation is common in AML and MDS patients. Azacytidine is a DNA methylation transferase inhibitor that can re-express tumor suppressor genes in leukemia cells. Venetoclax is a selective BCL-2 inhibitor, which has antitumor activity against a variety of hematological malignancies. The combination of the two drugs show a synergistic anti-tumor effect. The objective of this study is to evaluate the safety and efficacy of VEN-AZA regimen followed by Allo-HSCT in the treatment of high-risk MDS and high-risk or relapsed/refractory AML.

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation; Acute Myeloid Leukemia; Myelodysplastic Syndrome

Study Design

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

Study Groups

VEN+AZA+Modified BUCY

Group Type: EXPERIMENTAL

VEN+AZA+Modified BUCY

Intervention Type: DRUG

Venetoclax: 200mg/day*7days（It should be combined with triazole antifungal drugs).

Azacytidine: 75mg/ m²/day*7days.

Interventions

VEN+AZA+Modified BUCY

Venetoclax: 200mg/day*7days（It should be combined with triazole antifungal drugs).

Azacytidine: 75mg/ m²/day*7days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 8 to 65 years;

2. Diseases must be MDS and AML; high-risk MDS: int-2 risk, high risk by the IPSS; IPSS-R int-risk (> 3.5 points), high risk, very high risk; high risk,very high risk by the WPSS; high-risk or relapsed/refractory AML: (1) age≥60 years; (2) High white blood cell count at first diagnosis (WBC≥100*10^9/L); (3) secondary AML (previous history of MDS, myeloproliferative disease, or treatment-related AML, etc.); (4) Complicated with extramedullary leukemia, such as central nervous system leukemia, granulocytic sarcoma, hepatosenomegaly; （5）high risk factors and relapsed/refractory AML（reference 2022-AML-ELN guideline）（6）not in remission or ≥CR2 before transplantation;

3. Must need a bone marrow transplant;

4. Must have the ability to observe the efficacy and events;

5. Patient must have ability to understand and willingness to provide written informed consent prior to participation in the study and any related procedures being performed.

Exclusion Criteria

1. Age <8 or >65 years;

2. Uncontrolled bacterial, viral, fungal, or other infection before conditioning regimen;

3. Pregnant or lactating females;

4. Current participation in another clinical trial;

5. Contra-indication to one of the drug of the regimen;

6. Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo the agents included in the conditioning regimen.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Depei Wu Wu, MD

Role: STUDY_CHAIR

The First Affiliated Hospital of Soochow University

Locations

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiaowen Tang, MD

Role: CONTACT

xwtang1020@163.com

+86-512-67781851

Depei Wu, MD

Role: CONTACT

wudepei@163.com

+86-512-67781851

Facility Contacts

Xiaowen Tang, PhD

Role: primary

xwtang1020@163.com

67781525

Other Identifiers

VA+mBUCY-01

Identifier Type: -

Identifier Source: org_study_id