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

Zhongming Zhang

Status and phase: Completed; Phase 4

Conditions: Graft-versus-host Disease (GVHD); Beta-Thalassemia Major

Treatments: Drug: Basiliximab,; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT02342145

gxmuh-2014-14

Details and patient eligibility

About

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.

Full 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.

Enrollment: 205 patients

Sex: All

Ages: 2 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. a diagnosis of TM with hemoglobin electrophoresis, a genetic diagnosis of -thalassemia by DNA analysis, and blood transfusion dependence;
2. a cardiac ejection fraction >50%;
3. normal pulmonary function tests and pulmonary examination results;
4. normal kidney function.

Exclusion criteria

1. aspartate aminotransferase level >4- fold the upper limit of normal range in our institution's laboratory criteria;
2. uncontrolled bacterial, viral, or fungal infection;
3. positive serology for HIV;
4. cytomegalovirus (CMV) or Epstein-Barr virus (EBV) copy number >200 copies/mL in blood by quantitative PCR. Patients positive for hepatitis C or hepatitis B virus were also excluded.

(8) Other circumstances which do not meet the inclusion criteria

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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205 participants in 2 patient groups

group A

Experimental group

Description:

The patients were used FK506 (0.03mg/kg/day), Methotrexate (15mg/m2 on +1d, 10mg/m2 on +3d, +6d, +11d), Mycophenolate Mofetil (0.25g/d, days-1 to 90) and Basiliximab (use 10mg for weight under 35kg, 20mg for over 35kg, 0d and +4d) for prevention of acute graft-versus-host-disease.

Treatment:

Drug: Mycophenolate mofetil

Drug: Methotrexate

Drug: Tacrolimus

Drug: Basiliximab,

group B

Active Comparator group

Description:

The patients were used FK506 (0.03mg/kg/day), Methotrexate (15mg/m2 on +1d, 10mg/m2 on +3d, +6d, +11d), Mycophenolate Mofetil (0.25g/d, days-1 to 90) for prevention of acute graft-versus-host-disease.

Treatment:

Drug: Mycophenolate mofetil

Drug: Methotrexate

Drug: Tacrolimus