Efficacy and Safety of Venetoclax and Azacitidine Combined With Low-Intensity Homoharringtonine Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Intermediate/High-Risk Newly Diagnosed Acute Myeloid Leukemia

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This study is a single-center, single-arm, prospective phase II clinical trial evaluating the efficacy and safety of the VAH (Venetoclax and Azacitidine combined with Homoharringtonine) regimen, followed by allo-HSCT for intermediate and high-risk AML. Eligible patients receive two cycles of the VAH chemotherapy regimen. If minimal residual disease (MRD) is negative after these two cycles, patients proceed to the transplantation process. If MRD remains positive, patients receive an additional two cycles of the VAH regimen. Upon achieving MRD negativity, they then proceed to the transplantation process. The conditioning regimen includes fludarabine at 30 mg/m²/day from day -7 to day -3 (5 days), cytarabine at 1-1.5 g/m²/day from day -7 to day -3 (5 days), and busulfan at 3.2 mg/kg/day from day -5 to day -3 (3 days). Conditioning begins on day -6, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year. If disease relapse is suspected during the follow-up period, bone marrow or extramedullary relapse site examinations will be conducted at any time. The primary endpoint is the 1-year and 2-year overall survival (OS). Secondary endpoints include the complete response (CR) rate after 1 and 2 cycles of chemotherapy; 1-year and 2-year disease-free survival (DFS) following the achievement of CR through induction therapy; cumulative relapse rate; non-relapse mortality (NRM); incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant; and the cumulative incidence of chronic GVHD within 1 year and 2 years post-transplant.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 55
Healthy Volunteers: f
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• Age between 18 and 55 years, inclusive, regardless of gender.

• Diagnosed with AML (excluding APL) according to the 2022 International Consensus Classification (ICC) for AML \[1\].

• Evaluated as intermediate/high-risk AML based on the 2022 ELN AML guidelines (see Appendix 1).

• No prior treatment for acute leukemia, including hypomethylating agents used for leukemia or myelodysplastic syndromes (MDS), except for hydroxyurea.

• Patients must have a suitable hematopoietic stem cell donor.

• Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2.

• ECOG (Eastern Cooperative Oncology Group) performance status: 0-2.

• Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements:

‣ Serum creatinine ≤ 1.5x ULN (the upper limit of normal);

⁃ Cardiac function: Ejection fraction ≥ 50%;

⁃ Baseline oxygen saturation \> 92%;

⁃ Total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 2.0 x ULN;

⁃ Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 (Forced Expiratory Volume in 1 second) ≥ 50%.

‣ 9\) Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form.

Locations
Other Locations
China
Shanghai General hospital,Shanghai Jiao Tong University School of Medicine
RECRUITING
Shanghai
Contact Information
Primary
Xianmin Song, MD
shongxm@139.com
13501672508
Time Frame
Start Date: 2024-07-02
Estimated Completion Date: 2028-07-01
Participants
Target number of participants: 56
Treatments
Experimental: VAH regimen combined with allo-HSCT
Eligible patients receive two cycles of the VAH chemotherapy regimen. If minimal residual disease (MRD) is negative after these two cycles, patients proceed to the transplantation process. If MRD remains positive, patients receive an additional two cycles of the VAH regimen. Upon achieving MRD negativity, they then proceed to the transplantation process.
Sponsors
Leads: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

This content was sourced from clinicaltrials.gov