Alefacept in Subjects With Steroid-Refractory Chronic Graft-versus-Host Disease

Phase 2

Terminated

Brief Summary: Alefacept is a drug tht may reduce the number of T cells in circulation. This drug has been used in the treatment of psoriasis, which is a skin disorder also caused by T cells, like chronic GVHD. Information from studies in psoriasis and in other patients with GVHD suggests that this drug may help to treat chronic GVHD. Chronic GVHD is a medical condition that can develop after allogeneic stem cell transplantation. It occurs when the donor immune cells (the "graft") attack and damage organs and tissue (the "host"). It is thought that T cells, a subtype of immune cells, are responsible for the tissue damage in chronic GVHD. In this research study we are looking to see how well Alefacept works in treating chronic GVHD that has not resolved after therapy with corticosteroids.

Detailed Description: * During the first week of treatment, participants will receive 2 doses of Alefacept intravenously (Day 1 and Day 4). During weeks 2-12, Alefacept will be given subcutaneously once weekly.

* On weeks 1, 2 and every other week through Week 12 of study treatment, participants will have a physical exam, blood tests, and be asked general health and specific questions about any problems they may be having.

* Every other week, participants will be asked to complete a questionnaire about their physical symptoms, activity level and emotional well being.

Recruitment & Eligibility

Inclusion Criteria

18 years of age or older
Diagnosed with cGVHD according to NIH criteria
Active cGVHD despite treatment with corticosteroids AND one additional immunosuppressive agent for at least 4 weeks, within 52 weeks of enrollment.
Subject is a recipient of related or unrelated BMT or PBSCT
Subject underwent transplantation at least 6 months prior to enrollment
Subject is on stable immunosuppressive regimen for 2 weeks prior to enrollment. Adjustment of immunosuppressive medications to maintain a therapeutic level is permitted.
Female of child bearing potential must have a negative pregnancy test prior to first dose of alefacept and must agree to practice effective contraception during the study. Men must also agree to use adequate contraception prior to study entry and for the duration of the study.
Meets medication restriction requirements and agrees to follow medications restrictions during study.

Exclusion Criteria

Received donor lymphocyte infusions in the preceding 100 days
Currently undergoing ECP
Subject is recipient of related or unrelated UCB
Subject has bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia or cryptogenic organizing pneumonia as the sole manifestation of cGVHD
Uncontrolled intercurrent active infection.
Absolute neutrophil count < 1000/L
AST, ALT or total bilirubin > 2x institutional upper limit of normal unless this is a manifestation of GVHD
Recurrent or progressive malignancy at any time after HCT, as applicable for the individual malignancy
Subject was in any clinical study within the last 30 days
Receipt of 5 or more prior agents to treat cGVHD
Known hypersensitivity to alefacept or any components of the study medication
Known to be positive for human immunodeficiency virus (HIV) antibodies
Currently enrolled in any other study for chronic GVHD treatment and receiving treatment under the study or previous participation in this study.
Pregnant or nursing
Concurrent illness which, in the opinion of the Investigator, may interfere with treatment or evaluation of safety

Arm && Interventions

Group	Intervention	Description
Alefacept	Alefacept	Alefacept iv

Primary Outcome Measures

Name	Time	Method
Efficacy	2 years	Proportion of patients with a favorable response, defined as a complete or partial remission at week 12 as compared to baseline in subjects with steroid refractory cGVHD.

Secondary Outcome Measures

Name	Time	Method
Safety of Alefacept Infusions in Patients With Chronic GVHD.	2 years	Assess the safety of alefacept in this patient population. The number of adverse events (including hematological and non-hematological safety events) will be used for safety assessment.

Locations (3): Fred Hutch Cancer Research Center
🇺🇸
Seattle, Washington, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States