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

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05823714

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Allogeneic Hematopoietic Stem Cell Transplantation Acute Myeloid Leukemia Myelodysplastic Syndrome	Drug: VEN+AZA+Modified BUCY	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Venetoclax + Azacytidine Followed by Modified BUCY Conditioning Regimen for High-risk Myelodysplastic Syndromes (MDS) and High-risk or Relapsed/Refractory Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

Actual Study Start Date :

Jan 20, 2022

Anticipated Primary Completion Date :

Jan 20, 2025

Anticipated Study Completion Date :

Jan 20, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VEN+AZA+Modified BUCY	Drug: VEN+AZA+Modified BUCY Venetoclax: 200mg/day7days（It should be combined with triazole antifungal drugs). Azacytidine: 75mg/ m²/day7days.

Arm

Intervention/Treatment

Experimental: VEN+AZA+Modified BUCY

Drug: VEN+AZA+Modified BUCY

Venetoclax: 200mg/day*7days（It should be combined with triazole antifungal drugs). Azacytidine: 75mg/ m²/day*7days.

Outcome Measures

Primary Outcome Measures

disease-free survival (DFS) [3 years after transplantation]
It is measured from the time from randomization to the first of relapse or death.
overall survival (OS) [3 years after transplantation]
It is measured from the time of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.

Secondary Outcome Measures

veno-occlusive disease (VOD) [3 years after transplantation]
incidence of veno-occlusive disease (VOD) events (refer to modified Seattle Criteria of VOD)
graft-versus-host disease (GvHD) [3 years after transplantation]
incidence and severity of acute (aGvHD) and chronic graft-versus-host disease (cGvHD) (aGvHD refer to Glucksberg Criteria and cGvHD refer to the National Institutes of Health Consensus)
transplant related mortality (TRM) [3 years after transplantation]
cumulative incidence of transplant related mortality
Regimen related toxicity [3 years after transplantation]
Number of participants with conditioning regimen related toxicity

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 8 to 65 years;
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;
Must need a bone marrow transplant;
Must have the ability to observe the efficacy and events;
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:

Age <8 or >65 years;
Uncontrolled bacterial, viral, fungal, or other infection before conditioning regimen;
Pregnant or lactating females;
Current participation in another clinical trial;
Contra-indication to one of the drug of the regimen;
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.