Combination of Alemtuzumab and Rituximab at Low-doses in Refractory Chronic Graft-Versus-Host Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether low-doses alemtuzumab and rituximab combination are effective in the treatment of chronic graft-versus-host disease (GVHD) after first-line therapy failure.

Detailed Description
-----------------
Graft-versus-host disease (GVHD) is the most common long-term complication in patients who underwent allogeneic transplantation. First-line therapy for chronic GVHD is based on immunosuppressive agents (usually cyclosporine and corticosteroids) achieving satisfactory response in around 30% of patients. There is no ideal second-line treatment for chronic GVHD; however, numerous studies have been published with therapeutic options such as alemtuzumab (anti-CD52) and rituximab (anti-CD20). This is a prospective, longitudinal, nonrandomized study in which alemtuzumab and rituximab will be administered at low-doses to patients with refractory chronic GVHD. Clinical response will be evaluated based on the Working Group Report 2006, published by the National Institute of Health Consensus. Follow-up sessions will be weekly for four weeks, every two weeks until achieve response, and finally every four weeks.

Official Title
-----------------
Combination of Alemtuzumab (Anti-CD52) and Rituximab (Anti-CD20) at Low-doses in Chronic Graft Versus Host Disease Treatment After First-line Therapy Failure.

Conditions
-----------------
Graft vs Host Disease

Intervention / Treatment
-----------------
* Drug: Alemtuzumab and rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with chronic graft-versus-host disease. Patients over 18 years old. Patients who received first-line treatment with no response (failure), relapse or steroid dependance. Exclusion Criteria: Patients with active bacterial or viral infections. Patients with hematologic disease progression. Patient's intolerance to drugs.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alemtuzumab and rituximab<br>Patients with chronic GVHD after first-line therapy failure will receive Alemtuzumab at 10mg subcutaneously daily for 3 doses (days 1, 2 and 3) Rituximab at 100mg intravenously weekly for 4 doses (days 4, 11, 18 and 25. THE STUDY HAVE ONLY ONE ARM. | Drug: Alemtuzumab and rituximab<br>* Alemtuzumab at 10mg subcutaneously daily for 3 doses (days 1, 2 and 3) Rituximab at 100mg intravenously weekly for 4 doses (days 4, 11, 18 and 25<br>* Other names: Rituxan;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response of Patients With Refractory Chronic GVHD Based on the Working Group Report 2006. | Overall response of participants to alemtuzumab and rituximab combination at day +30, +90 and +365 of follow-up | 30, 90 and 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side Effects | Percentage of participants who experienced side effects | 365 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Graft vs Host Disease, Alemtuzumab, Rituximab, Low-dose, Alemtuzumab and rituximab combination