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

January 16, 2015 updated by: Affiliated hospital of guangxi medical university,china

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Fujian
      • Fuzhou, Fujian, China, 350000
        • Recruiting
        • Union Hospital of Fujian Medical University
      • Xia'men, Fujian, China, 361000
        • Recruiting
        • the zhongshan hospital of Xiamen University
    • Guangxi
      • Nanning, Guangxi, China, 530021
        • Recruiting
        • The Affiliated Hospital OF Guangxi Medical University
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • Affiliated Drum Tower Hospital, Nanjing medical university
    • Yunnan
      • Kunming, Yunnan, China, 650000
        • Recruiting
        • Kunming General Hospital of Chengdu Military Region

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Simulect
  • chimeric mouse-human antiCD25
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:
  • 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 Names:
  • Ametnopterin
Drug: Mycophenolate mofetil
Mycophenolate mofetil was used 0.25g qd from 0d to 3 months for prevention of graft-versus-host-disease.
Other Names:
  • 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 Names:
  • 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 Names:
  • Ametnopterin
Drug: Mycophenolate mofetil
Mycophenolate mofetil was used 0.25g qd from 0d to 3 months for prevention of graft-versus-host-disease.
Other Names:
  • cellcept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
acute graft-versus-host disease incidence
Time Frame: two years
two years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: two years
two years
Implantation rate
Time Frame: two years
two years
Transplanted-related mortality
Time Frame: two years
two years
Infection incidence
Time Frame: two years
two years
Chronic graft-versus-host-disease incidence
Time Frame: two years
two years
Disease-free-survival
Time Frame: two years
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Affiliated hospital of guangxi medical university,china

Collaborators

Zhongshan Hospital Xiamen University
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Union hospital of Fujian Medical University
Kunming general Hospital of Chengdu Military Region

Investigators

  • Principal Investigator: yongrong lai, PhD, Guangxi Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2014

Primary Completion (Anticipated)

June 1, 2016

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

January 14, 2015

First Submitted That Met QC Criteria

January 16, 2015

First Posted (Estimate)

January 19, 2015

Study Record Updates

Last Update Posted (Estimate)

January 19, 2015

Last Update Submitted That Met QC Criteria

January 16, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • gxmuh-2014-14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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