Alefacept for Prevention of Graft Versus Host Disease (GVHD)

April 19, 2015 updated by: Hadassah Medical Organization

An Investigator Initiated Double Blind Randomized Study of Alefacept Treatment Prevention of Graft Versus Host Disease in Myeloablative Stem Cell Transplantation

Alefacept (AMEVIVE®) is an immunosuppressive dimeric fusion protein. It was shown to interfere with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Alefacept was evaluated in two randomized, double-blind, placebo-controlled studies in adults with chronic (>1 year) plaque psoriasis and a minimum body surface area involvement of 10% who were candidates for or had previously received systemic therapy or phototherapy. 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.

Graft versus host disease (GVHD) is the most ominous side effect of allogeneic 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.

It was shown that CD2 depletion of allografts could prevent GVHD. Alefacept was never systemically tried in GVHD but A phase II study of BTI-322, a rat monoclonal IgG2b directed against the CD2 antigen in steroid-refractory acute GVHD showed a total response rate of 55%. We showed that alefacept might have a beneficial effect in controlling steroid resistant aGVHD and chronic GVHD. It was also shown to dramatically change the nature of transfusion associated GVHD.

Study Overview

Status

Terminated

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 3

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

      • Jerusalem, Israel, 91120
        • Department of Stem Cell Transplantation & Cancer Immunotherapy

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

14 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient age 14-75 years old with a disease necessitating allogeneic SCT.
  2. In order to increase security, only full matched donors will be allowed and must be willing and capable of donating peripheral blood stem cells preferably, or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated.
  3. Patients must sign written informed consents.
  4. Patients must have an ECOG PS ≤ 2; creatinine < 2.0 mg/dl; ejection fraction > 40%; DLCO > 50% of predicted; serum bilirubin < 3 gm/dl; elevated GPT or GOT > 3 x normal values.

Exclusion Criteria:

  1. Not fulfilling any of the inclusion criteria.
  2. Active life-threatening infection.
  3. Overt untreated infection.
  4. Hypersensitivity to alefacept.
  5. HIV seropositivity, Hepatitis B or C antigen positivity with active hepatitis.
  6. Pregnant or lactating women.
  7. Donor contraindication (HIV seropositive confirmed by western blot).
  8. Hepatitis B antigenemia.
  9. Evidence of bone marrow disease.
  10. Unable to donate bone marrow or peripheral blood due to concurrent medical condition.
  11. Inability to comply with study requirements.

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
these patients will receive the same treatment as group A, without alefacept
Experimental: 1
Alefacept
Alefacept
Other Names:
  • Alefacept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Acute GVHD occurrence.
Time Frame: 100d
100d
Acute GVHD grading.
Time Frame: 100d
100d

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to acute GVHD.
Time Frame: 100d
100d
Chronic GVHD occurrence.
Time Frame: 180d
180d
Chronic GVHD grading.
Time Frame: 180d
180d
Engraftment/graft rejection.
Time Frame: 21d
21d
Overall survival.
Time Frame: 180d
180d
Disease free survival.
Time Frame: 180d
180d
Infections.
Time Frame: 180d
180d
Transplant-related mortality (TRM).
Time Frame: 180d
180d
Immune reconstitution
Time Frame: 180d
180d
Toxicity assessment according to the Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame: 180d
180d

Collaborators and Investigators

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

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.

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

June 1, 2006

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

July 31, 2006

First Submitted That Met QC Criteria

August 6, 2006

First Posted (Estimate)

August 8, 2006

Study Record Updates

Last Update Posted (Estimate)

April 21, 2015

Last Update Submitted That Met QC Criteria

April 19, 2015

Last Verified

December 1, 2010

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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