Clinical trial NCT05809167: Venetoclax+Azacytidine+Modified BUCY Conditioning Regimen for Acute Lymphoblastic Leukemia Undergoing Allo-HSCT
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Allogeneic Hematopoietic Stem Cell Transplantation
Acute Lymphoblastic Leukemia
Keywords: venetoclax
azacytidine
hematopoietic stem cell transplantation
acute lymphoblastic leukemia
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2023-04-12
Enrollment: 55
Sex: ALL
Minimum age (years): 8
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: disease-free survival (DFS)
timeFrame: 3 years after transplantation
measure: overall survival (OS)
timeFrame: 3 years after transplantation
Secondary outcomes:
measure: veno-occlusive disease (VOD)
timeFrame: 3 years after transplantation
measure: graft-versus-host disease (GvHD)
timeFrame: 3 years after transplantation
measure: transplant related mortality (TRM)
timeFrame: 3 years after transplantation
measure: Regimen related toxicity
timeFrame: 3 years after transplantation
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu Wu, MD
role: STUDY_CHAIR
References: