NCT02342145

Efficacy of Basiliximab in the Prevention of Acute Graft-versus-host Disease in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation Therapy for Thalassemia Major

Efficacy of Basiliximab in the Prevention of Acute Graft-versus-host Disease in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation Therapy for Thalassemia Major Treatment: a Multi-center, Open, Randomized, Controlled Clinical Study

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 205 (actual)
• Sponsor: Zhongming Zhang · Academic / Other
• Sex: All
• Age: 2 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the basiliximab for prevention of graft-versus-host disease in unrelated allo-genetic hematopoietic stem cell transplantation for thalassemia major. The objective was to evaluate the effect and safety of basiliximab for acute graft-versus-host disease.

Detailed description

Allo-geneic stem cell transplantation(allo-HSCT) cure thalassemia major by destroying the original hematopoietic and immune systems with a large dose of chemotherapy, rebuilding a new system to correct the abnormal hematopoietic globin chain synthesis which leads to hemolysis. Currently, it is the only curative means. According to donors, allo-HSCT could be sibling allogeneic hematopoietic stem cell transplantation and unrelated allogeneic hematopoietic stem cell transplantation(URD-HSCT). URD-HSCT could expand the range of treatment among β-thalassemia major patients. As recently reported , 68 cases of thalassemia patients at the median age of 15 (2 to 37 ) received unrelated donor BMT. According to Pesaro rating classification, 14 patients were attributed to type Ⅰ, 16 cases Ⅱ type , 38 cases type III, overall survival and thalassemia free survival rates were 79.3% and 65.8%. A survey among 59 evaluable patients indicated that grade Ⅱ \~ Ⅳ aGVHD occurred in 24 cases (40%) , in which 10 cases (17%) were grade Ⅲ \~ Ⅳ aGVHD. Similar results were seen in other reports, 21 patients received unrelated donor BMT, with a 2-year thalassemia free survival rate of 71%. GVHD happened in 3 cases, and 3 patients died. Our institution has conducted a total of 10 cases of URD-HSCT to treat severe thalassemia, using methotrexate + cyclosporine A+ mycophenolate mofetil to prevent graft-versus-host disease, 9 cases of disease-free survival, 1 case with graft rejection. Incidence of Ⅲ-Ⅳ severe acute graft-versus-host disease (aGVHD) was 20%. Severe aGVHD incidence was 20%. Our research group has found there is a high risk to develop aGVHD, especially severe aGVHD for heavy thalassemia patients who receive URD-HSCT, which seriously affects the prognosis and survival, while increasing medical costs and the financial burden on the patients' families. The key factor affecting URD-HSCT's success is GVHD. Thus effective prevention and treatment of GVHD is a prerequisite to ensure a successful transplant. CD25 is a humanized monoclonal IgG1,with murine anti-human IL-2RA chain complement determining region retained. IL-2RA chain expressed only on the surface of activated cytotoxic T cells, which could convert the IL-2R complexes into a higher affinity. The feature that IL-2RA distributes only on the surface of activated lymphocytes indicates it's a ideal target when designing the policy to scavenge antigen-specific allogeneic reactive T cells. In vitro experiments, CD25 monoclonal antibody binds specifically with IL-2RA+ cells by inhibiting IL-2 binding to its receptor competitively. Basiliximab has now been used as first-line medication for aGVHD treatment, as well as the combined prevention of hematologic malignancies URD-HSCT treatment . However as for thalassemia major URD-HSCT, few cases have been reported. This study was aimed at the high incidence of aGVHD, especially severe aGVHD in thalassemia major URD-HSCT. Basiliximab was added to the original prevention program. The aGVHD incidence, implantation rate, transplant-related mortality, infection incidence would be observed. It is hopeful to reduce the aGVHD incidence after URD-HSCT and promote curative effect.

Conditions

• Beta-Thalassemia Major
• Graft-versus-host Disease (GVHD)

Interventions

Type	Name	Description
DRUG	Basiliximab,	Basiliximab was used on 0d (after transplantation) and +4d (10mg for weight under 35kg, 20mg for over 35kg) .
DRUG	Tacrolimus	Specifically Tacrolimus was used by intravenous drip infusion on 0.03mg/kg dosage from -1d and change to 0.1mg/kg oral when gastrointestinal function recovers. The blood concentrations of cyclosporine A was maintained 5-10 ng/ml.
DRUG	Methotrexate	Methotrexate was used 15mg/m2 on +1d and 10mg/m2 on +3d,+6d,+11d by intravenous for prevention of graft-versus-host-disease.
DRUG	Mycophenolate mofetil	Mycophenolate mofetil was used 0.25g per day from -1d to 90d for prevention of graft-versus-host-disease.

Timeline

• Start date: 2015-04-01
• Primary completion: 2022-08-20
• Completion: 2022-08-20
• First posted: 2015-01-19
• Last updated: 2025-06-18

Locations

3 sites across 1 country: China