Alefacept for Prevention of Graft Versus Host Disease (GVHD)

NCT00361413 | Terminated Phase 3

• 1 other identifier: MYS-01-HMO-CTIL
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Versus Host Disease

Keywords

Stem cell transplantation; GVHD; Graft Versus Host Disease

Outcome Measures

Primary Outcomes (2)

• Acute GVHD occurrence.

  100d

• Acute GVHD grading.

  100d

Secondary Outcomes (10)

• Time to acute GVHD.

  100d

• Chronic GVHD occurrence.

  180d

• Chronic GVHD grading.

  180d

• Engraftment/graft rejection.

  21d

• Overall survival.

  180d

Study Arms (2)

1

EXPERIMENTAL

Alefacept

Drug: Alefacept (AMEVIVE®)

2

PLACEBO COMPARATOR

Drug: control group

Interventions

Alefacept (AMEVIVE®) DRUG

Alefacept

Also known as: Alefacept

1

control group DRUG

these patients will receive the same treatment as group A, without alefacept

2

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Department of Stem Cell Transplantation & Cancer Immunotherapy

Jerusalem, 91120, Israel

Location

Related 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. doi: 10.1038/sj.bmt.1705185.

  PMID: 16247429 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Alefacept; Control Groups

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

CD58 Antigens; Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Membrane Proteins; Recombinant Fusion Proteins; Recombinant Proteins; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Michael Y Shapira, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 31, 2006
• First Posted: August 8, 2006
• Study Start: June 1, 2006
• Primary Completion: July 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 21, 2015

Record last verified: 2010-12

Locations

IL (1)