- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00361413
Alefacept for Prevention of Graft Versus Host Disease (GVHD)
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
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Jerusalem, Israel, 91120
- Department of Stem Cell Transplantation & Cancer Immunotherapy
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient age 14-75 years old with a disease necessitating allogeneic SCT.
- 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.
- Patients must sign written informed consents.
- 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:
- Not fulfilling any of the inclusion criteria.
- Active life-threatening infection.
- Overt untreated infection.
- Hypersensitivity to alefacept.
- HIV seropositivity, Hepatitis B or C antigen positivity with active hepatitis.
- Pregnant or lactating women.
- Donor contraindication (HIV seropositive confirmed by western blot).
- Hepatitis B antigenemia.
- Evidence of bone marrow disease.
- Unable to donate bone marrow or peripheral blood due to concurrent medical condition.
- Inability to comply with study requirements.
Study Plan
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:
|
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
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MYS-01-HMO-CTIL
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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Clinical Trials on Alefacept (AMEVIVE®)
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Astellas Pharma IncCompletedChronic Plaque PsoriasisUnited States, Canada
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Uni-PharmaBiogenCompletedChronic Plaque Psoriasis
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Astellas Pharma IncBiogenCompletedChronic Plaque PsoriasisUnited States, Canada
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Astellas Pharma IncAstellas Pharma Canada, Inc.Terminated
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University of California, San FranciscoCompletedModerate to Severe PsoriasisUnited States
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Astellas Pharma IncCompletedPsoriasisUnited States, Bulgaria, Latvia
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Astellas Pharma IncTerminated