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

Sponsor

The Korean Society of Hematopoietic Stem Cell Transplantation (Other)

Overall Status

Unknown status

CT.gov ID

NCT00472225

Collaborator

Hoffmann-La Roche (Industry)

Enrollment

Locations

Arm

Duration (Months)

4.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Steroid-Refractory Chronic GVHD	Drug: Rituximab	Phase 2

Detailed Description

STUDY OBJECTIVES

Primary Endpoints: To assess the response rate
Secondary End points
To evaluate the discontinuation of corticosteroid
To assess the quality of life

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 Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

May 1, 2007

Anticipated Primary Completion Date :

May 1, 2008

Anticipated Study Completion Date :

May 1, 2009

Arms and Interventions

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

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

Outcome Measures

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 [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Kyungpook University Hospital	Daegu	Kyungsang-do	Korea, Republic of
2	Busan Baik Hospital	Busan		Korea, Republic of
3	Busan National University Hospital	Busan		Korea, Republic of
4	Chun Nam National University Hospital	Gwangju		Korea, Republic of
5	Samsung Medical Center	Seoul		Korea, Republic of	136-710
6	Seoul National University	Seoul		Korea, Republic of
7	Soon Chun Hyang Hospital	Seoul		Korea, Republic of
8	The Catholic University of Korea	Seoul		Korea, Republic of
9	Yonsei University Hospital	Seoul		Korea, Republic of