Alefacept for Prevention of Graft Versus Host Disease (GVHD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00361413
Recruitment Status : Terminated (company withdrawal of the drug)
First Posted : August 8, 2006
Last Update Posted : April 21, 2015
Information provided by:
Hadassah Medical Organization

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Drug: Alefacept (AMEVIVE®) Drug: control group Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
Official Title: An Investigator Initiated Double Blind Randomized Study of Alefacept Treatment Prevention of Graft Versus Host Disease in Myeloablative Stem Cell Transplantation
Study Start Date : June 2006
Actual Primary Completion Date : July 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1
Drug: Alefacept (AMEVIVE®)
Other Name: Alefacept
Placebo Comparator: 2 Drug: control group
these patients will receive the same treatment as group A, without alefacept

Primary Outcome Measures :
  1. Acute GVHD occurrence. [ Time Frame: 100d ]
  2. Acute GVHD grading. [ Time Frame: 100d ]

Secondary Outcome Measures :
  1. Time to acute GVHD. [ Time Frame: 100d ]
  2. Chronic GVHD occurrence. [ Time Frame: 180d ]
  3. Chronic GVHD grading. [ Time Frame: 180d ]
  4. Engraftment/graft rejection. [ Time Frame: 21d ]
  5. Overall survival. [ Time Frame: 180d ]
  6. Disease free survival. [ Time Frame: 180d ]
  7. Infections. [ Time Frame: 180d ]
  8. Transplant-related mortality (TRM). [ Time Frame: 180d ]
  9. Immune reconstitution [ Time Frame: 180d ]
  10. Toxicity assessment according to the Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: 180d ]

Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00361413

Department of Stem Cell Transplantation & Cancer Immunotherapy
Jerusalem, Israel, 91120
Sponsors and Collaborators
Hadassah Medical Organization
Principal Investigator: Michael Y Shapira, MD Hadassah Medical Organization

Responsible Party: Michael Shapira, MD, Hadassah University Hospital Identifier: NCT00361413     History of Changes
Other Study ID Numbers: MYS-01-HMO-CTIL
First Posted: August 8, 2006    Key Record Dates
Last Update Posted: April 21, 2015
Last Verified: December 2010

Keywords provided by Hadassah Medical Organization:
Stem cell transplantation
Graft Versus Host Disease

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Dermatologic Agents