Clinical trial NCT05823714: Venetoclax+Azacytidine+Modified BUCY Conditioning Regimen for Acute Myeloid Leukemia and Myelodysplastic Syndromes Undergoing Allo-HSCT
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Allogeneic Hematopoietic Stem Cell Transplantation
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Keywords: venetoclax
azacytidine
hematopoietic stem cell transplantation
acute myeloid leukemia
myelodysplastic syndrome
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2023-04-21
Enrollment: 70
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 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.

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.

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: