Alefacept for Prevention of Graft Versus Host Disease (GVHD)

Graft Versus Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00361413
• Other study ID #: MYS-01-HMO-CTIL
• Status: Terminated
• Phase: Phase 3
• First received: July 31, 2006
• Last updated: April 19, 2015
• Start date: June 2006
• Est. completion date: December 2013

Study information

• Verified date: December 2010
• Source: Hadassah Medical Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: December 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Alefacept (AMEVIVE®)
Alefacept
• control group
these patients will receive the same treatment as group A, without alefacept

Locations

Country	Name	City	State
Israel	Department of Stem Cell Transplantation & Cancer Immunotherapy	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

References & Publications (1)

Shapira MY, Resnick IB, Bitan M, Ackerstein A, Tsirigotis P, Gesundheit B, Zilberman I, Miron S, Leubovic A, Slavin S, Or R. Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report. Bone Marrow Transplant. 2005 Dec;36(12):1097-101. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute GVHD occurrence.		100d	No
Primary	Acute GVHD grading.		100d	No
Secondary	Time to acute GVHD.		100d	No
Secondary	Chronic GVHD occurrence.		180d	No
Secondary	Chronic GVHD grading.		180d	No
Secondary	Engraftment/graft rejection.		21d	Yes
Secondary	Overall survival.		180d	No
Secondary	Disease free survival.		180d	No
Secondary	Infections.		180d	Yes
Secondary	Transplant-related mortality (TRM).		180d	Yes
Secondary	Immune reconstitution		180d	Yes
Secondary	Toxicity assessment according to the Common Terminology Criteria for Adverse Events (CTCAE)		180d	Yes