Clinical trial NCT00397332: Alefacept for Chronic Graft Versus Host Disease
Official title: An Investigator Initiated Open-label and Explorative Study of Alefacept Treatment for Chronic Extensive Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Resistant Chronic GVHD
Keywords: GVHD
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2006-11-09
Enrollment: 20
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: GVHD response.
timeFrame: 6m
measure: Time to GVHD response
timeFrame: 6m
Secondary outcomes:
measure: Overall survival.
timeFrame: 6m
measure: Disease free survival.
timeFrame: 6m
measure: Occurrence of infections.
timeFrame: 6m
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Department of Stem cell Transplantation & Cancer immunotherapy; Cell Therapy & Transplantation Biology Research Laboratory, Hadassah University Hospital
Study officials:
affiliation: Department of Stem cell Transplantation & Cancer immunotherapy; Cell Therapy & Transplantation Biology Research Laboratory, Hadassah University Hospital
name: Michael Y Shapira, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.