Resistant Chronic GVHD Clinical Trial
Official title:
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.
| Status | Completed |
| Enrollment | 20 |
| Est. completion date | July 2013 |
| Est. primary completion date | January 2013 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | N/A to 70 Years |
| Eligibility |
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 |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Israel | Department of Stem cell Transplantation & Cancer immunotherapy; Cell Therapy & Transplantation Biology Research Laboratory, Hadassah University Hospital | Jerusalem |
| Lead Sponsor | Collaborator |
|---|---|
| Hadassah Medical Organization |
Israel,
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | GVHD response. | 6m | No | |
| Primary | Time to GVHD response | 6m | No | |
| Secondary | Overall survival. | 6m | Yes | |
| Secondary | Disease free survival. | 6m | Yes | |
| Secondary | Occurrence of infections. | 6m | Yes |