Alefacept for Chronic Graft Versus Host Disease

April 19, 2015 updated by: Hadassah Medical Organization

An Investigator Initiated Open-label and Explorative Study of Alefacept Treatment for Chronic Extensive Graft Versus Host Disease

Alefacept (AMEVIVE®) is an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fcof IgG1. Alefacept is produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) mammalian cell expression system. It was shown to interfere with lymphocyte activation. Alefacept was evaluated in two randomized, double-blind, placebo-controlled studies in adults with chronic plaque psoriasis. Each course consisted of once-weekly administration for 12 weeks of placebo or alefacept. The response to alefacept was significantly better in both studies. In both studies, onset of response to alefacept treatment (defined as at least 50% reduction of baseline Psoriasis Area and Severity Index (PASI)) began 60 days after the start of therapy. With one course of therapy, the median duration of response (defined as maintenance of a 75% or greater reduction in PASI) was 3.5 months for alefacept treated patients and 1 month for placebo-treated patients. Most patients who had responded to either alefacept or placebo maintained a 50% or greater reduction in PASI through the 3-month observation period.

Graft versus host disease (GVHD) is the most ominous side effect of allogenic stem cell transplantation (SCT). It causes severe inflammatory process, which is usually located to the skin, gut and liver. Treatment of GVHD consists of various immuno-suppressive and immuno-modulating drugs, including steroids, cyclosporine, tacrolimus, methotrexate etc. These drugs unfortunately can also cause severe immunologic failure that makes the patient prone to infection and malignancy, and other medication-specific side effects. In spite of this effect on the immune system, not all of the patients achieve control of GVHD, which usually rapidly leads to death. Despite the use of innovative immunosuppressive modalities, the prognosis of steroid resistant GVHD is usually poor. In the following study we will evaluate the effect of alefacept on steroid unresponsive cGVHD.

Study Overview

Status

Completed

Conditions

Resistant Chronic GVHD

Intervention / Treatment

Drug: Alefacept

Study Type

Interventional

Enrollment (Anticipated)

Phase

Phase 2
Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Israel
- - Jerusalem, Israel, 91120
    - Department of Stem cell Transplantation & Cancer immunotherapy; Cell Therapy & Transplantation Biology Research Laboratory, Hadassah University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

No age limit
Resistant chronic GVHD

Exclusion Criteria:

Not fulfilling any of the inclusion criteria
Active life-threatening infection
Inability to comply with study requirements.
Known hypersensitivity to alefacept.
Active malignant disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
GVHD response. Time Frame: 6m	6m
Time to GVHD response Time Frame: 6m	6m

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival. Time Frame: 6m	6m
Disease free survival. Time Frame: 6m	6m
Occurrence of infections. Time Frame: 6m	6m

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hadassah Medical Organization

Investigators

Principal Investigator: Michael Y Shapira, MD, Department of Stem cell Transplantation & Cancer immunotherapy; Cell Therapy & Transplantation Biology Research Laboratory, Hadassah University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Shapira MY, Resnick IB, Bitan M, Ackerstein A, Tsirigotis P, Gesundheit B, Zilberman I, Miron S, Leubovic A, Slavin S, Or R. Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report. Bone Marrow Transplant. 2005 Dec;36(12):1097-101. doi: 10.1038/sj.bmt.1705185.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

November 8, 2006

First Submitted That Met QC Criteria