Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids (NRR)
RATIONALE: Efalizumab may be an effective treatment for graft-versus-host disease of the skin caused by a donor stem cell transplant.
PURPOSE: This clinical trial is studying the side effects and how well efalizumab works in treating patients with graft-versus-host disease of the skin that did not respond to previous steroids.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
|Official Title:||Weekly Subcutaneous Efalizumab for the Treatment of Steroid Refractory Graft-Versus-Host Disease of the Skin and Liver|
- Number of Subjects Experiencing Adverse Events [ Time Frame: 120 days ]
The primary objective of this exploratory study is to evaluate the general tolerability of efalizumab in patients suffering from steroid refractory GVHD
Subjects will be evaluated for drug toxicity each visit. Toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) common criteria.
- Degree of Skin Involvement by GVHD Using Two Digital Photography Techniques. [ Time Frame: 120 days ]
Estimate of the percentage of body surface area involved by GVHD using two digital photography techniques and computerized image analyses:
- Digital photography and body surface area calculations: A total of 12 digital photographs were obtained from different body regions using systematic digital imaging and computerized image analysis.
- Body surface area calculations: Using National Institutes of Health image software, each body region will be manually traced and the total area of the traced area determined. Using a similar technique, each part of the region that is involved by a GVHD rash will also be traced and its area measured. The areas involved by rash will then be summed, and finally divided by the total area of the region. In so doing, the percentage of each region that is involved by GVHD will be determined.
- Exploratory Assessment of the Staining of Cutaneous Tissues for LFA-1, ICAM-1, CD4, CD8, and Possibly CD20 [ Time Frame: 57 days ]Numerical scoring system for both LFA-1 and ICAM-1 expression which could then be used in a larger phase II trial to correlate clinical response rates to pathological findings.
- Overall Complete Response Rate [ Time Frame: 57 days ]To assess the overall complete response rate on study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab. A complete response (CR) was defined as the total resolution of skin disease, and a partial response was defined as >=50% reduction in the proportion of total body surface area involved by rash.
- Complete Cutaneous Response Rate [ Time Frame: On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab ]The complete disappearance of all signs of cutaneous graft-versus-host disease. Complete cutaneous response rate + partial cutaneous response rate
- Overall Hepatic Response Rate [ Time Frame: On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab ]The normalization of the total serum bilirubin to <2mg/dL
|Study Start Date:||December 2006|
|Study Completion Date:||October 2008|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
All patients on study will receive a total of 8 injections of efalizumab
Efalizumab will be administered as a subcutaneous injection once a week for 8 weeks (total of 8 doses). First efalizumab injection will be dosed at 0.7mg/kg. Subsequent weekly injections given on days 8-50 will be dosed at
Other Name: Raptiva
- Assess the general safety of efalizumab in patients with cutaneous graft-vs-host disease (GVHD).
- Study the feasibility of digital imaging to objectively quantify cutaneous GVHD.
- Evaluate the feasibility of serial skin biopsies to monitor disease response to efalizumab in patients with cutaneous GVHD.
- Assess the overall complete response rate in patients treated with this drug.
- Assess the overall cutaneous response rate (complete cutaneous response rate and partial cutaneous response rate) in patients treated with this drug.
- Assess the overall hepatic response rate (complete hepatic response rate and partial hepatic response rate) in patients treated with this drug.
- Assess the duration of any responses observed.
- Assess the effect of this drug on overall patient survival.
- Use the preliminary efficacy and toxicity data collected in this small exploratory study to decide on the appropriateness of a larger, subsequent phase II trial to more formally assess toxicity and efficacy of this drug in this patient population.
- Collect pharmacokinetic data on this drug in these patients.
OUTLINE: Patients receive efalizumab subcutaneously once weekly for 8 weeks (total of 8 doses).
Digital photographs of body regions are taken for determination of disease involved body surface area. Skin biopsies are obtained before and after treatment and analyzed for lymphocyte function associated antigen (LFA-1), intercellular adhesion molecule (ICAM-1), cluster of differentiation 4, 8, and possibly 20 (CD4, CD8, CD20) by immunohistochemistry.
After completion of study therapy, patients are followed at 1 and 9 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00489216
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599-7295|
|Principal Investigator:||Thomas C. Shea, MD||UNC Lineberger Comprehensive Cancer Center|