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

Beta-Thalassemia Major Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02342145
• Other study ID #: gxmuh-2014-14
• Status: Recruiting
• Phase: Phase 4
• First received: January 14, 2015
• Last updated: January 16, 2015
• Start date: June 2014
• Est. completion date: December 2018

Study information

• Verified date: January 2015
• Source: First Affiliated Hospital of Guangxi Medical University
• Contact: yongrong lai, PhD
• Phone: 86-771-5356510
• Email: laiyongrong[@]263.net
• Is FDA regulated: No
• Health authority: China: National Health and Family Planning Commission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2018
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Age: 2 to 18 years old

2. Gender: Male or female

3. Thalassemia major

4. Donor and recipient sides 10/10 consistency

5. Unrelated allogeneic peripheral blood stem cell transplantation

6. In good general condition , ECOG score = 1

7. Normal heart function: ejection fraction = 50%

8. 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

9. Enrolled subjects or their families signed informed consent

Exclusion Criteria:

1. severe infection uncontrolled before transplantation

2. severe allergic on Basiliximab (anaphylactic shock or laryngeal edema)

3. sibling allogeneic hematopoietic stem cell transplantation

4. Cardiac dysfunction (ejection fraction <50%)

5. Renal insufficiency (serum creatinine> 130umol / L)

6. Hepatic dysfunction (total bilirubin> 34umol / L, ALT, AST> 2 times the upper limit of normal)

7. Previously history of allogeneic hematopoietic stem cell transplantation

8. Other circumstances which do not meet the inclusion criteria

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Beta-Thalassemia
• Beta-Thalassemia Major
• Graft vs Host Disease
• Thalassemia

Intervention

Drug:
• Basiliximab,
Basiliximab was used 10mg each time on 0d(after transplantation) and +4 d .
• 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.
• Methotrexate
Methotrexate was used 15mg/m2 on +1d and 10mg/m2 on +3,+6,+11d by intravenous for prevention of graft-versus-host-disease.
• Mycophenolate mofetil
Mycophenolate mofetil was used 0.25g qd from 0d to 3 months for prevention of graft-versus-host-disease.

Locations

Country	Name	City	State
China	Union hospital of fujian medical university	Fuzhou	Fujian
China	Kunming general hospital of chengdu military region	Kunming	Yunnan
China	Affiliated Drum Tower Hospital, Nanjing medical university	Nanjing	Jiangsu
China	The affiliated hospital of guangxi medical university	Nanning	Guangxi
China	the zhongshan hospital of Xiamen University	Xia'men	Fujian

Sponsors (5)

Lead Sponsor	Collaborator
Affiliated hospital of guangxi medical university,china	Kunming general Hospital of Chengdu Military Region, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The zhongshan Hospital xiamen University, Union hospital of Fujian Medical University

Country where clinical trial is conducted

China, 

References & Publications (5)

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. — View 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 — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	acute graft-versus-host disease incidence		two years	Yes
Secondary	Implantation rate		two years	Yes
Secondary	Transplanted-related mortality		two years	Yes
Secondary	Infection incidence		two years	Yes
Secondary	Chronic graft-versus-host-disease incidence		two years	Yes
Secondary	Overall survival		two years	Yes
Secondary	Disease-free-survival		two years	Yes