Alefacept for Prevention of Graft Versus Host Disease (GVHD)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by Hadassah Medical Organization.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT00361413
First received: July 31, 2006
Last updated: March 1, 2011
Last verified: December 2010
  Purpose

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 Intervention Phase
Graft Versus Host Disease
Drug: Alefacept (AMEVIVE®)
Drug: control group
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
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

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Acute GVHD occurrence. [ Time Frame: 100d ] [ Designated as safety issue: No ]
  • Acute GVHD grading. [ Time Frame: 100d ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to acute GVHD. [ Time Frame: 100d ] [ Designated as safety issue: No ]
  • Chronic GVHD occurrence. [ Time Frame: 180d ] [ Designated as safety issue: No ]
  • Chronic GVHD grading. [ Time Frame: 180d ] [ Designated as safety issue: No ]
  • Engraftment/graft rejection. [ Time Frame: 21d ] [ Designated as safety issue: Yes ]
  • Overall survival. [ Time Frame: 180d ] [ Designated as safety issue: No ]
  • Disease free survival. [ Time Frame: 180d ] [ Designated as safety issue: No ]
  • Infections. [ Time Frame: 180d ] [ Designated as safety issue: Yes ]
  • Transplant-related mortality (TRM). [ Time Frame: 180d ] [ Designated as safety issue: Yes ]
  • Immune reconstitution [ Time Frame: 180d ] [ Designated as safety issue: Yes ]
  • Toxicity assessment according to the Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: 180d ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: July 2006
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Alefacept
Drug: Alefacept (AMEVIVE®)
Alefacept
Other Name: Alefacept
Placebo Comparator: 2 Drug: control group
these patients will receive the same treatment as group A, without alefacept

  Eligibility

Ages Eligible for Study:   14 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00361413

Contacts
Contact: Michael Y Shapira, MD 972-2-6778351 shapiram@hadassah.org.il

Locations
Israel
Department of Stem Cell Transplantation & Cancer Immunotherapy Recruiting
Jerusalem, Israel, 91120
Contact: Michael Y Shapira, MD    972-2-6778351    shapiram@hadassah.org.il   
Sponsors and Collaborators
Hadassah Medical Organization
Investigators
Principal Investigator: Michael Y Shapira, MD Hadassah Medical Organization
  More Information

Publications:
Responsible Party: Michael Shapira, MD, Hadassah University Hospital
ClinicalTrials.gov Identifier: NCT00361413     History of Changes
Other Study ID Numbers: MYS-01-HMO-CTIL
Study First Received: July 31, 2006
Last Updated: March 1, 2011
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

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

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Alefacept
Dermatologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014