Clinical trial NCT00136396: Rituximab Therapy for Steroid-Refractory Chronic Graft Versus Host Disease
Official title: An Open Label, Phase I/II Trial of Rituximab Therapy for Steroid-Refractory Chronic Graft vs. Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Graft vs Host Disease
Keywords: Steroid-refractory Chronic Graft vs. Host Disease
Chronic Graft vs. Host Disease
GVHD
steroid-refractory
rituximab
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
First posted: 2005-08-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if rituximab is a safe and effective therapy for steroid-refractory chronic graft versus host disease (GVHD).

Detailed description: Patients will receive rituximab intravenously one time per week for four consecutive weeks. Once therapy is completed, the patient will have weekly visits with their physician for four more weeks, at which they will complete a simple questionnaire designed to evaluate the severity of chronic graft versus host disease.

At the end of the eighth week on the study (4 weeks of study treatment and 4 weeks of observation), patients will be evaluated to determine whether their chronic graft versus host disease (GVHD) has resolved.

If chronic graft versus host disease has resolved entirely, the patient will be monitored for the remainder of the year.

If after the initial eight weeks on the study the patient still has symptoms or signs of GVHD, they may receive a second four week study treatment.

If the patients' chronic GVHD reappears after receiving either one or two courses of rituximab, a third and final four week course of medication can be given provided it has been at least eight weeks since the last dose.

Blood tests will be performed at the beginning of the study, after 8 weeks on the study, after 16 weeks on the study and at the end of 1 year.

Eligibility criteria: Inclusion Criteria:

* Recipients of matched related, matched unrelated, or mismatched stem cell transplantation
* At least 180 days since allogeneic stem cell transplantation procedure
* Patients must have steroid-refractory chronic GVHD, defined as having persistent signs and symptoms despite the use of prednisone
* Stable dose of corticosteroids for 4 weeks prior to enrollment
* Adequate bone marrow function: absolute neutrophil count (ANC) \> 500/mm; platelets \> 20,000 ul
* Adequate renal function: creatinine \< 3.0 mg/dl
* Adequate hepatic function: bilirubin \< 3.0 mg/dl; AST \< 90 IU

Exclusion Criteria:

* Prednisone requirement greater than 2 mg/kg/day or equivalent
* Known life-threatening sensitivity to rituximab or other anti-B cell antibody.
* Prior exposure to any new immunosuppressive medication in the preceding 4 weeks prior to enrollment.
* Active, uncontrolled infection
* Evidence of natural exposure to hepatitis B or C.
* Active malignant disease relapse
* Donor lymphocyte infusion within the preceding 100 days.
* Life expectancy of less than 3 months.
* Pregnancy or lactation
* Evidence of HIV seropositivity

Primary outcomes:
measure: To determine the safety and efficacy of up to three four week courses of rituximab in steroid-refractory chronic GVHD
timeFrame: 2 years
Secondary outcomes:
measure: To determine the effects of rituximab therapy on quality of life of patients with steroid-refractory GVHD
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Corey S. Cutler, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D, Klickstein LB, Levin J, Miller K, Reynolds C, Macdonell R, Pasek M, Lee SJ, Ho V, Soiffer R, Antin JH, Ritz J, Alyea E. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood. 2006 Jul 15;108(2):756-62. doi: 10.1182/blood-2006-01-0233. Epub 2006 Mar 21.