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

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ClinicalTrials.gov Identifier: NCT02342145
Recruitment Status : Unknown
Verified January 2015 by Affiliated hospital of guangxi medical university,china, First Affiliated Hospital of Guangxi Medical University.
Recruitment status was:  Recruiting
First Posted : January 19, 2015
Last Update Posted : January 19, 2015
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
Affiliated hospital of guangxi medical university,china, First Affiliated Hospital of Guangxi Medical University

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
Beta-Thalassemia Major Drug: Basiliximab, Drug: cyclosporine A Drug: Methotrexate Drug: Mycophenolate mofetil 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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 Start Date : June 2014
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : December 2018


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:
  • chimeric mouse-human antiCD25
  • Simulect

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 Name: cyclosporin

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 Name: Ametnopterin

Drug: Mycophenolate mofetil
Mycophenolate mofetil was used 0.25g qd from 0d to 3 months for prevention of graft-versus-host-disease.
Other Name: cellcept

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 Name: cyclosporin

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 Name: Ametnopterin

Drug: Mycophenolate mofetil
Mycophenolate mofetil was used 0.25g qd from 0d to 3 months for prevention of graft-versus-host-disease.
Other Name: cellcept




Primary Outcome Measures :
  1. acute graft-versus-host disease incidence [ Time Frame: two years ]

Secondary Outcome Measures :
  1. Implantation rate [ Time Frame: two years ]
  2. Transplanted-related mortality [ Time Frame: two years ]
  3. Infection incidence [ Time Frame: two years ]
  4. Chronic graft-versus-host-disease incidence [ Time Frame: two years ]
  5. Overall survival [ Time Frame: two years ]
  6. Disease-free-survival [ Time Frame: two years ]


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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02342145


Contacts
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Contact: yongrong lai, PhD 86-771-5356510 laiyongrong@263.net
Contact: zhongming zhang, MD 86-771-5356510 zzmmissyou@126.com

Locations
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China, Fujian
Union hospital of fujian medical university Recruiting
Fuzhou, Fujian, China, 350000
the zhongshan hospital of Xiamen University Recruiting
Xia'men, Fujian, China, 361000
China, Guangxi
The affiliated hospital of guangxi medical university Recruiting
Nanning, Guangxi, China, 530021
Contact: yongrong lai, PhD    86-771-5356746    laiyongrong@263.net   
China, Jiangsu
Affiliated Drum Tower Hospital, Nanjing medical university Recruiting
Nanjing, Jiangsu, China, 210000
China, Yunnan
Kunming general hospital of chengdu military region Recruiting
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
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Principal Investigator: yongrong lai, PhD Guangxi Medical University

Publications of Results:
Other Publications:
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Responsible Party: Affiliated hospital of guangxi medical university,china, the affiliated hospital of guangxi medical university, First Affiliated Hospital of Guangxi Medical University
ClinicalTrials.gov Identifier: NCT02342145     History of Changes
Other Study ID Numbers: gxmuh-2014-14
First Posted: January 19, 2015    Key Record Dates
Last Update Posted: January 19, 2015
Last Verified: January 2015
Keywords provided by Affiliated hospital of guangxi medical university,china, First Affiliated Hospital of Guangxi Medical University:
beta-Thalassemia major
Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
Graft vs Host Disease
Immune System Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Cyclosporine
Mycophenolic Acid
Methotrexate
Cyclosporins
Basiliximab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors