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

Open-Labelled, Multicenter Phase II Study of Rituximab in Patients With Steroid-Refractory Chronic Graft-Versus-Host Disease

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.

Study Overview

• Status: Unknown
• Conditions: Steroid-Refractory Chronic GVHD
• Intervention / Treatment: Drug: Rituximab

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

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Busan National University Hospital
  • Busan, Korea, Republic of
    • Busan Baik Hospital
  • Gwangju, Korea, Republic of
    • Chun Nam National University Hospital
  • Seoul, Korea, Republic of
    • Seoul National University
  • Seoul, Korea, Republic of, 136-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Soon Chun Hyang Hospital
  • Seoul, Korea, Republic of
    • The Catholic University of Korea
  • Seoul, Korea, Republic of
    • Yonsei University Hospital
  • Kyungsang-do
    • Daegu, Kyungsang-do, Korea, Republic of
      • Kyungpook University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 72 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Mabthera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Response evaluation will be perfomed every 4 weeks during the maintenance of rituximab (the 12th, 16th, 20th, 24st, 36th and 52th week).

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity	1 year
Steroid tapering	Within one year after start the first dose of rituximab
Quality of life	Baseline, the 8th and 52th week.

Collaborators and Investigators

• Sponsor: The Korean Society of Hematopoietic Stem Cell Transplantation
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Jong-Ho Won, MD, Soon Chun Hyang Hospital, Seoul, Korea

Publications and helpful links

Helpful Links

• Home page of the Korean society of hematopoietic stem cell transplantation

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Anticipated): May 1, 2008
• Study Completion (Anticipated): May 1, 2009

Study Registration Dates

• First Submitted: May 10, 2007
• First Submitted That Met QC Criteria: May 10, 2007
• First Posted (Estimate): May 11, 2007

Study Record Updates

• Last Update Posted (Estimate): February 24, 2009
• Last Update Submitted That Met QC Criteria: February 20, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: rituximab; Chronic graft-versus-host disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: KHSCT-01-2007