Study of Rituximab in Patients With Steroid-Refractory Chronic Graft-Versus-Host Disease

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by The Korean Society of Hematopoietic Stem Cell Transplantation.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
The Korean Society of Hematopoietic Stem Cell Transplantation
ClinicalTrials.gov Identifier:
NCT00472225
First received: May 10, 2007
Last updated: February 20, 2009
Last verified: February 2009
  Purpose

Chronic GVHD is the most common late complication following allogeneic stem cell transplantation. It has features resembling autoimmune disorders such as scleroderma, primary biliary cirrhosis, bronchiolitis obliterans, chronic immunodeficiency etc. Thus, chronic GVHD can lead to debilitating complications such as joint contractures, blindness, end-stage lung disease, etc so that chronic GVHD has a major impact both on survival as well as quality of life. Although its pathogenesis is still poorly unclear, it has been reported since 2000 that B cell-mediated immunity may also contribute to development of chronic GVHD other than T cells. Thus, targeting against B cell may be a useful treatment strategy in the treatment of chronic GVHD.

The purpose of this study is to determine whether rituximab, an anti-CD20 monoclonal kimeric antibody is effective in the treatment of chronic graft-versus-host disease (chronic GVHD) refractory to steroid.


Condition Intervention Phase
Steroid-Refractory Chronic GVHD
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-Labelled, Multicenter Phase II Study of Rituximab in Patients With Steroid-Refractory Chronic Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by The Korean Society of Hematopoietic Stem Cell Transplantation:

Primary Outcome Measures:
  • Complete response (CR) : Resolution of all signs and symptoms of chronic GVHD Partial response (PR) : Improvement (at least 1 clinical score reduction) in 1 or more organs of involvement and no evidence of worsening in any organ [ Time Frame: Response evaluation will be perfomed every 4 weeks during the maintenance of rituximab (the 12th, 16th, 20th, 24st, 36th and 52th week). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Steroid tapering [ Time Frame: Within one year after start the first dose of rituximab ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: Baseline, the 8th and 52th week. ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 42
Study Start Date: May 2007
Estimated Study Completion Date: May 2009
Estimated Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Rituximab treatment arm
Drug: Rituximab

Rituximab Induction: Rituximab 375 mg/m2 weekly IV for 4 consecutive weeks

Rituximab Maintenance: Rituximab 375 mg/m2 monthly IV for 4 consecutive months

Other Name: Mabthera

Detailed Description:
  1. STUDY OBJECTIVES

    • Primary Endpoints: To assess the response rate
    • Secondary End points

      • To evaluate the discontinuation of corticosteroid
      • To assess the quality of life
  2. Treatment schedule

    • The BSA on the date of every treatment cycle may be used as the same value of baseline BSA, if change of body weight is within 10% of baseline body weight.
    • Treatment schedule consists of induction and maintenance therapy as follows

      • Induction - Rituximab 375 mg/m2 weekly IV for 4 consecutive weeks
      • Maintenance - Rituximab 375 mg/m2 monthly IV for 4 consecutive months
  Eligibility

Ages Eligible for Study:   3 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All recipients underwent allogeneic stem cell transplantation for haematologic disorders
  • All recipients diagnosed as chronic GVHD according to diagnostic criteria proposed by National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD

    • The presence of one diagnostic sign Or
    • The presence of one distinctive sign (Appendix 1B) with laboratory or histopathologic confirmation in the same or other organ if diagnostic feature is not present
  • All patients with chronic GVHD have at least moderate score based on the global scoring system of chronic GVHD
  • Recipients refractory or resistant to therapy with corticosteroid

    • Patients had chronic GVHD with the same severity during the last one month while they had received the equivalent of prednisone ≥0.5mg/kg per day or 1mg/kg every other day at least for 30 days or longer
  • Informed consent
  • Other concomitant medication

    • Patients treated with other immunosuppressive agents (cyclosporine, thalidomide etc) as a combination therapy with corticosteroid must be receiving a dosage that has been stable for at least 1 month prior to screening.

Exclusion Criteria:

  • Recipients received donor lymphocyte infusions in the preceding 100 days
  • Serious comorbid diseases
  • Life expectancy of less than 1 month
  • Age < 2 years and > 75 years
  • Pregnant or intended to become pregnant
  • Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00472225

Locations
Korea, Republic of
Kyungpook University Hospital
Daegu, Kyungsang-do, Korea, Republic of
Busan National University Hospital
Busan, Korea, Republic of
Busan Baik Hospital
Busan, Korea, Republic of
Chun Nam National University Hospital
Gwangju, Korea, Republic of
Seoul National University
Seoul, Korea, Republic of
Yonsei University Hospital
Seoul, Korea, Republic of
Soon Chun Hyang Hospital
Seoul, Korea, Republic of
The Catholic University of Korea
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of, 136-710
Sponsors and Collaborators
The Korean Society of Hematopoietic Stem Cell Transplantation
Hoffmann-La Roche
Investigators
Principal Investigator: Jong-Ho Won, MD Soon Chun Hyang Hospital, Seoul, Korea
  More Information

Additional Information:
No publications provided

Responsible Party: Jong Ho Won M.D., Ph.D., The Korean Society of Hematopoietic Stem Cell Transplantation
ClinicalTrials.gov Identifier: NCT00472225     History of Changes
Other Study ID Numbers: KHSCT-01-2007
Study First Received: May 10, 2007
Last Updated: February 20, 2009
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by The Korean Society of Hematopoietic Stem Cell Transplantation:
Chronic graft-versus-host disease
rituximab

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014