Study of Chidamide for Steroid-resistant/Steroid-dependent Severe cGVHD
Status:
Recruiting
Trial end date:
2024-05-31
Target enrollment:
Participant gender:
Summary
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is one of the most important
and effective methods for the treatment of hematologic malignancies.Chronic graft-versus-host
disease (cGVHD) is a serious complication of allogeneic stem cell transplantation with few
effective options available after failure of corticosteroids. It is a leading cause of late
nonrelapse mortality for transplant patients, also contributing to morbidity and a decrease
in quality of life.Corticosteroids, the standard frontline treatment, are typically
administered for a median of 2 to 3 years, leading to substantial morbidity. An effort to
decrease corticosteroid doses has led to their use in combination with other
immunosuppressants, such as cyclosporine, tacrolimus, and sirolimus, in frontlineor
second-line settings, despite a lack of clinical evidence supporting additional efficacy
after combining these agents with corticosteroids. B and T cells play a rolein the
pathophysiology of cGVHD. Previous studies have shown that low-dose histone deacetylase
inhibitors (HDACi) have a negative immune regulation in GVHD while maintain the GVL effect.
Chidamide is one of new HDACis in China, the previous studies suggested that low dose
Chidamide could reduce condition of cGVHD mice by regulating the immune homeostasis of
follicular helper T (Tfh) cells. Chidamide also has effects on the regulation of antigen
presenting cells, the activation donor T cells, the release of proinflammatory cytokines and
the function of Treg cells. Furthermore, low-dose Chidamide has the potential to maintain GVL
effects. In preclinical models,Chidamide reduced severity of cGVHD. Based on the biological
rationale and preclinical data, a study was designed to evaluate the safety and efficacy of
Chidamide in patients with cGVHD who was steroid-resistant/steroid-dependent .
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
The First Affiliated Hospital of Soochow University