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Viral Infection in Haploidentical HSCT With ATG for Acute Graft-versus-host Disease Prophylaxis

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Nanfang Hospital of Southern Medical University
Sponsor:
Collaborators:
Peking University People's Hospital
Guangxi Medical University
Southern Medical University, China
Guangzhou General Hospital of Guangzhou Military Command
Information provided by (Responsible Party):
Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier:
NCT01883180
First received: June 14, 2013
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to compare the incidences of GVHD and viral infections in haploidentical hematopoietic stem cell transplant recipients receiving different dose of antithymocyte globulin (ATG) for acute graft-versus-host disease(aGVHD) prophylaxis. Our first objective was to investigate the optimal dose of ATG for aGVHD and second object was to evaluate the effect of different dose of ATG on post-transplant viral infection.


Condition Intervention Phase
Hematopoietic Stem Cell Transplantation
Antithymocyte Globulin
Viral Infection
Drug: ATG
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Viral Infection in Haploidentical Hematopoietic Stem Cell Transplantation With Different Dose of Antithymocyte Globulin for Acute Graft-versus-host Disease Prophylaxis

Resource links provided by NLM:


Further study details as provided by Nanfang Hospital of Southern Medical University:

Primary Outcome Measures:
  • Incidence of aGVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Acute GVHD was graded according to standard criteria.


Secondary Outcome Measures:
  • Incidence of Epstein-Barr virus(EBV)and cytomegalovirus(CMV) infections [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    EBV and CMV infections include EBV and CMV viremia, and associated diseases.

  • Drug-related adverse events of ATG [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Drug-related adverse events include acute toxicity and late side effects.

  • Immune reconstitution [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Immune reconstitution is performed every 3 months after transplantation.

  • Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Survival includes overall and disease-free survival within 2 years after transplantation.

  • Incidence of chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Chronic GVHD was assessed in patients alive after day 100.


Estimated Enrollment: 100
Study Start Date: June 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATG 7.5mg/kg
ATG 7.5mg/kg group refers to treatment with ATG in the total dose of 7.5mg/kg.
Drug: ATG
ATG will be intravenously infused via a central venous catheter in 3 or 4 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include cytosine arabinoside (Ara-C), busulfan (Bu),cyclophosphamide (Cy), Semustine(Me-CCNU), and ATG. All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF), and short-term methotrexate for aGVHD prevention.
Experimental: ATG 10mg/kg
ATG 10mg/kg group refers to treatment with ATG in the total dose of 10mg/kg.
Drug: ATG
ATG will be intravenously infused via a central venous catheter in 3 or 4 days, from day -4 or -3 until day 0. The other conditioning drugs administered before transplantation include cytosine arabinoside (Ara-C), busulfan (Bu),cyclophosphamide (Cy), Semustine(Me-CCNU), and ATG. All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF), and short-term methotrexate for aGVHD prevention.

Detailed Description:

Allogeneic hematopoietic stem cell transplantation (allo-HSCT)is the only therapeutic option for many hematological malignancies. Unfortunately, about 75% of patients who require allo-HSCT lack human leukocyte antigen (HLA)-matched donors. The alternative is hematopoietic stem cells from an HLA-mismatched family donor. However, this strategy, which is called haploidentical HSCT, may be associated with high risk of early death and severe GVHD.

Opportunistic infections are common complications after allo-HSCT. Due to the absence of effective preventive and therapeutic drugs for most viruses, viral infections has become one of the most important causes of death. The immunosuppression regimen including ATG has been shown effective to prevent severe GVHD in haploidentical HSCT. But this strategy delays immune reconstitution, and therefore increase the risk of viral infection.

The optimal dose of the different ATG preparations with respect to prevention of GvHD is not fully understood today. The total doses between 6 mg/kg to 15 mg/kg are effective for prevention of GVHD, but the dose above 10 mg/kg may increase the development of viral infection.

In this trial, we will focus on the incidence of aGVHD and viral infections in patients treated with 7.5mg/kg or 10mg/kg of ATG. The incidence of GVHD and viral infections will be compared between different dose arms.

  Eligibility

Ages Eligible for Study:   14 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A patient age of 14-65 years
  • Haploidentical hematopoietic stem cell transplant recipient
  • Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

  • Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
  • Patients with any conditions not suitable for the trial (investigators' decision)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01883180

Contacts
Contact: Ren Lin, MD +86-020-61641613 lansinglinren@hotmail.com

Locations
China, Guangdong
Department of Hematology,Nanfang Hospital, Southern Medical University Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Ren Lin, MD    +86-020-61641613    lansinglinren@hotmail.com   
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
Peking University People's Hospital
Guangxi Medical University
Southern Medical University, China
Guangzhou General Hospital of Guangzhou Military Command
Investigators
Principal Investigator: Qifa Liu, MD Nanfang Hospital of Southern Medical University
  More Information

Publications:
Responsible Party: Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT01883180     History of Changes
Other Study ID Numbers: NFEC-201304-K1
Study First Received: June 14, 2013
Last Updated: August 27, 2014
Health Authority: China: Ethics Committee

Keywords provided by Nanfang Hospital of Southern Medical University:
haploidentical hematopoietic Stem Cell Transplantation
Antithymocyte globulin
viral infection

Additional relevant MeSH terms:
Communicable Diseases
Graft vs Host Disease
Infection
Virus Diseases
Immune System Diseases
Antilymphocyte Serum
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014