Efficacy of Basiliximab in the Prevention of Acute Graft-versus-host Disease in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation Therapy for Thalassemia Major
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: group A The patients were used cycloaporine A:2mg/kg combined with methotrexate 15mg/m2 +1d，10mg/m2 +3,+6,+11d,mycophenolate mofetil: 0.25g/d, -1d to 90d and basiliximab: 10mg each time, 0d and +4 d for prevention of graft-versus-host-disease. |
Drug: Basiliximab,
Basiliximab was used 10mg each time on 0d(after transplantation) and +4 d .
Other Names:
Drug: cyclosporine A
Specifically cyclosporine A was used by intravenous drip infusion on 2mg/kg dosage from -1d and change to 5mg/kg twice oral when gastrointestinal function recovers. The blood concentrations of cyclosporine A was maintained 150-250ng/ml.
Other Names:
Drug: Methotrexate
Methotrexate was used 15mg/m2 on +1d and 10mg/m2 on +3,+6,+11d by intravenous for prevention of graft-versus-host-disease.
Other Names:
Drug: Mycophenolate mofetil
Mycophenolate mofetil was used 0.25g qd from 0d to 3 months for prevention of graft-versus-host-disease.
Other Names:
|
| Experimental: group B The patients were used cyclosporine A 2mg/kg,methotrexate,15mg/m2 +1d，10mg/m2 +3,+6,+11d,mycophenolate mofetil: 0.25g/d, -1d to 90d for prevention of graft-versus-host-disease. |
Drug: cyclosporine A
Specifically cyclosporine A was used by intravenous drip infusion on 2mg/kg dosage from -1d and change to 5mg/kg twice oral when gastrointestinal function recovers. The blood concentrations of cyclosporine A was maintained 150-250ng/ml.
Other Names:
Drug: Methotrexate
Methotrexate was used 15mg/m2 on +1d and 10mg/m2 on +3,+6,+11d by intravenous for prevention of graft-versus-host-disease.
Other Names:
Drug: Mycophenolate mofetil
Mycophenolate mofetil was used 0.25g qd from 0d to 3 months for prevention of graft-versus-host-disease.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- acute graft-versus-host disease incidence [two years]
Secondary Outcome Measures
- Implantation rate [two years]
- Transplanted-related mortality [two years]
- Infection incidence [two years]
- Chronic graft-versus-host-disease incidence [two years]
- Overall survival [two years]
- Disease-free-survival [two years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age: 2 to 18 years old
-
Gender: Male or female
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Thalassemia major
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Donor and recipient sides 10/10 consistency
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Unrelated allogeneic peripheral blood stem cell transplantation
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In good general condition , ECOG score ≤ 1
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Normal heart function: ejection fraction ≥ 50%
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Normal liver and renal function: Serum bilirubin ≤ 35μmol / L, AST / ALT less than 2 times the upper limit , serum creatinine under 2 times the upper limit
-
Enrolled subjects or their families signed informed consent
Exclusion Criteria:
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severe infection uncontrolled before transplantation
-
severe allergic on Basiliximab (anaphylactic shock or laryngeal edema)
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sibling allogeneic hematopoietic stem cell transplantation
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Cardiac dysfunction (ejection fraction <50%)
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Renal insufficiency (serum creatinine> 130umol / L)
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Hepatic dysfunction (total bilirubin> 34umol / L, ALT, AST> 2 times the upper limit of normal)
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Previously history of allogeneic hematopoietic stem cell transplantation
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Other circumstances which do not meet the inclusion criteria
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Union hospital of fujian medical university | Fuzhou | Fujian | China | 350000 |
| 2 | the zhongshan hospital of Xiamen University | Xia'men | Fujian | China | 361000 |
| 3 | The affiliated hospital of guangxi medical university | Nanning | Guangxi | China | 530021 |
| 4 | Affiliated Drum Tower Hospital, Nanjing medical university | Nanjing | Jiangsu | China | 210000 |
| 5 | Kunming general hospital of chengdu military region | Kunming | Yunnan | China | 650000 |
Sponsors and Collaborators
- Affiliated hospital of guangxi medical university,china
- Union hospital of Fujian Medical University
- Zhongshan Hospital Xiamen University
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- Kunming general Hospital of Chengdu Military Region
Investigators
- Principal Investigator: yongrong lai, PhD, Guangxi Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
- Hu LD, Chen H, Jiang M, Li BT, Yu ZY, Li YH. [The role of CD25 antibody in unrelated hematopoietic stem cell transplantation]. Zhonghua Nei Ke Za Zhi. 2005 Nov;44(11):848-50. Chinese.
- Smiers FJ, Krishnamurti L, Lucarelli G. Hematopoietic stem cell transplantation for hemoglobinopathies: current practice and emerging trends. Pediatr Clin North Am. 2010 Feb;57(1):181-205. doi: 10.1016/j.pcl.2010.01.003. Review.
- Wang HX, Yan HM, Wang ZD, Xue M, Liu J, Guo ZK. Haploidentical hematopoietic stem cell transplantation in hematologic malignancies with G-CSF mobilized bone marrow plus peripheral blood stem cells grafts without T cell depletion: a single center report of 29 cases. Leuk Lymphoma. 2012 Apr;53(4):654-9. doi: 10.3109/10428194.2011.624225. Epub 2011 Dec 5.
- gxmuh-2014-14