Venetoclax+Azacytidine+Modified BUCY Conditioning Regimen for Acute Lymphoblastic Leukemia Undergoing Allo-HSCT

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05809167

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.1

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 or relapsed/refractory acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Condition or Disease	Intervention/Treatment	Phase
Allogeneic Hematopoietic Stem Cell Transplantation Acute Lymphoblastic Leukemia	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 acute lymphoblastic leukemia. 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 ALL 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. Multiple case reports the efficacy of Venetoclax-based regimens in patients with ALL is encouraging. The objective of this study is to evaluate the feasibility, safety and efficacy of VEN-AZA bridging allogeneic hematopoietic stem cell transplantation in the treatment of high-risk ALL.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Venetoclax (VEN)+Azacytidine (AZA) Followed by Modified BUCY Conditioning Regimen for High Risk or Refractory/Relapsed Acute Lymphoblastic Leukemia 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 regimen related toxicity as assessed by CTCAE v4.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 14 to 65 years;
Diagnosis of high-risk or relapsed/refractory acute lymphoblastic leukemia at the time of transplant.
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 <14 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