Study of Chidamide for Steroid-resistant/Steroid-dependent Severe cGVHD

• Status: Recruiting
• Trial end date: 2024-05-31
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The First Affiliated Hospital of Soochow University

Criteria

Inclusion Criteria:

1. The disease progressed after at least 1 week of treatment with ≥ 1 mg/kg/d prednisone based immunosuppressive therapy;

2. The disease did not improve after at least 1 month of immunosuppressive therapy with ≥ 1 mg·kg once every 2 days or ≥ 0.5 mg/kg/d prednisone;

3. Gocorticoid dependence: Prednisone with > 0.25 mg/kg/d or > 0.5 mg·kg every 2 days after at least 8 weeks of glucocorticoid-based immunosuppressant therapy is required to prevent recurrence or progression.

4. Patients with severe glucocorticoid-resistant/dependent cGVHD who have poor response to second-line treatment drugs (mycophoranate, high-dose glucocorticoid, extracorporeal light therapy, sirolimus, imatinib, azathiopurine, thalidomide, rituximab, anti-CD25, etc.).

5. Ages 18-59

6. ECOG score 0-3

7. Expected survival longer than 6 months

8. The patient who signed the informed consent must be able to understand and willing to participate in the study, and must sign the informed consent.

Exclusion Criteria:

1. Basic diseases of important organs: such as myocardial infarction, chronic cardiac insufficiency, decompensated liver insufficiency, renal insufficiency, etc.;Clinically uncontrolled active infections (including bacterial, fungal or viral infections), but not those under effective medication;

2. Malignant tumors with other progression;

3. Cardiac dysfunction patients: ejection fraction (EF) < 30%, NYHA standard, cardiac dysfunction grade Ⅲ or above;

4. Pregnant or lactating women;

5. People undergoing clinical trials of other drugs;