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

Phase 2

Recruiting

• Conditions: Acute Lymphoblastic Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation
• Interventions: Drug: VEN+AZA+Modified BUCY

• Registration Number: NCT05809167
• Lead Sponsor: The First Affiliated Hospital of Soochow University

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).

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 Timeline

• Study Start: 2022-01-20
• Status Verified: 2023-02
• Study First Submitted: 2023-02-27
• Study First Submitted QC: 2023-04-10
• Last Update Submitted: 2023-04-10
• Study First Posted: 2023-04-12
• Last Update Posted: 2023-04-12
• Primary Completion: 2025-01-20
• Study Completion: 2026-01-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
VEN+AZA+Modified BUCY	VEN+AZA+Modified BUCY	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
veno-occlusive disease (VOD)	3 years after transplantation	incidence of veno-occlusive disease (VOD) events (refer to modified Seattle Criteria of VOD)

Trial Locations

Locations (1)

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China