Clinical trial NCT02342145: Efficacy of Basiliximab in the Prevention of Acute Graft-versus-host Disease in Unrelated Allogeneic Hematopoietic Stem Cell Transplantation Therapy for Thalassemia Major
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Beta-Thalassemia Major
Graft-versus-host Disease (GVHD)
Keywords: beta-Thalassemia major
Graft-versus-host disease
Basiliximab
Allogeneic hematopoietic stem cell transplantation
matched unrelated donors
Lead sponsor: First Affiliated Hospital of Guangxi Medical University
Sponsor class: OTHER
Collaborators: name: Liuzhou Workers Hospital
name: Hainan General Hospital
name: McMaster University
name: Guangxi Key Laboratory of Thalassemia Research
name: NHC Key Laboratory of Thalassemia Medicine
First posted: 2015-01-19
Enrollment: 205
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: grade II-IV acute graft-versus-host disease incidence
timeFrame: 100 days after matched unrelated donor hematopoietic stem cell transplantation.
Secondary outcomes:
measure: Implantation rate
timeFrame: three years
measure: Transplanted-related mortality
timeFrame: three years
measure: Infection incidence
timeFrame: three years
measure: Chronic graft-versus-host-disease incidence
timeFrame: five years
measure: Overall survival
timeFrame: three years
measure: Disease-free-survival
timeFrame: three years
Other outcomes:
Locations:
city: Liuzhou
country: China
facility: Liuzhou Worker's Hospital
state: Guangxi
city: Nanning
country: China
facility: The affiliated hospital of guangxi medical university
state: Guangxi
city: Haikou
country: China
facility: Hainan general Hospital
state: Hainan
Study officials:
affiliation: First Affiliated Hospital of Guangxi Medical University
name: yongrong lai, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Feng Z, Sun E, Lan H, Zhang C, Li Q, Zhu W. Unrelated donor bone marrow transplantation for beta-thalassemia major: an experience from China. Bone Marrow Transplant. 2006 Jan;37(2):171-4. doi: 10.1038/sj.bmt.1705193.
citation: Hongeng S, Pakakasama S, Chuansumrit A, Sirachainan N, Kitpoka P, Udomsubpayakul U, Ungkanont A, Jootar S. Outcomes of transplantation with related- and unrelated-donor stem cells in children with severe thalassemia. Biol Blood Marrow Transplant. 2006 Jun;12(6):683-7. doi: 10.1016/j.bbmt.2006.02.008.
citation: 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.
citation: 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.