Clinical trial NCT06626737: Dapagliflozin in Allo-HCT for aGVHD
Official title: Dapagliflozin for Preventing Acute Graft-versus-Host Disease in Allogeneic Hematopoietic Cell Transplantation: A Prospective, Single-Arm Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Graft-versus-host Disease (GVHD)
Keywords: Dapagliflozin
Graft-versus-host disease
Allogeneic hematopoietic cell transplantation
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2024-10-04
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to learn if Dapagliflozin could prevent acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) with haploidentical or unrelated donor and to assess its safety. The main questions it aims to answer are: Dose Dapagliflozin lower the cumulative incidence of aGVHD? What medical problems do participants undergoing allo-HCT from haploidentical or unrelated donor have when taking Dapagliflozin? Researchers will document the occurrence of graft-versus-host disease, hematopoietic reconstitution, survival rates and adverse effects. Participants will take Dapagliflozin every day in -1 to 14 days.


Eligibility criteria: Inclusion Criteria:

* Age 18 to 65 years old.
* Patients with hematologic malignancies indicated for allo-HCT and having a suitable haploidentical or unrelated donor.
* Willing to undergo myeloablative conditioning and graft-versus-host disease prophylaxis base on cyclosporin A and methotrexate.
* With Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
* Patients with prior use of Dapagliflozin or other hypoglycemic medications may switch to Dapagliflozin, contingent upon the treating physician's assessment of contraindications, will be eligible.
* Signing an informed consent form, having the ability to comply with study and follow-up procedures.

Exclusion Criteria:

* With other malignancies.
* With a previous history of autologous hematopoietic cell transplantation, allo-HCT or chimeric antigen receptor T-cell therapy.
* With a history of allergies to Dapagliflozin.
* With type 1 diabetes or a history of ketoacidosis.
* With a history of recurrent urinary tract infections.
* With severe organ dysfunction.
* With active hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection.
* In pregnancy or lactation period.
* With any conditions not suitable for the trial (investigators' decision).

Primary outcomes:
measure: Cumulative incidence of grade II-IV aGVHD
timeFrame: 100 days after transplantation.
Secondary outcomes:
measure: Cumulative incidence of grade III-IV aGVHD
timeFrame: 100 days after transplantation.
measure: Neutrophil reconstitution
timeFrame: up to 30 days.
measure: Platelet reconstitution
timeFrame: up to 100 days.
measure: Cumulative incidence of chronic graft-versus-host disease (cGVHD)
timeFrame: 1 year after transplantation.
measure: Overall survival
timeFrame: 1 year after transplantation.
measure: Cumulative incidence of relapse
timeFrame: 1 year after transplantation.
measure: Graft-versus-host disease-free relapse-free survival (GRFS)
timeFrame: 1 year after transplantation.
measure: Treatment related non-hematological grade 3 or higher adverse events
timeFrame: up to 100 days.
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
References:
citation: Cheng Q, Wang D, Lai X, Liu Y, Zuo Y, Zhang W, Lei L, Chen J, Liu H, Wang Y, Liu H, Zheng H, Wu D, Xu Y. The OTUD1-Notch2-ICD axis orchestrates allogeneic T cell-mediated graft-versus-host disease. Blood. 2023 Mar 23;141(12):1474-1488. doi: 10.1182/blood.2022017201.