Protocol Number: 04-N-0133

Title:

Effects of a T Cell-Depleting Monoclonal Antibody, Alemtuzumab, in Patients with Inclusion Body Myositis: A Pilot Clinicopathological Study

Number:

04-N-0133

Summary:

This study will examine the safety and effectiveness of alemtuzumab (Campath® (Registered Trademark)) for improving muscle strength in patients with sporadic inclusion body myositis (s-IBM). The most common inflammatory muscle disease in people over the age of 50, s-IBM progresses steadily, leading to severe weakness and wasting of the muscles in the arms and legs. The cause of s-IBM is not known, but it may be an autoimmune disease, in which the body's immune cells (white blood cells) attack and destroy parts of muscle. Alemtuzumab is a laboratory-made antibody currently approved to treat certain leukemias. It has also been used to treat patients with autoimmune conditions such as rheumatoid arthritis, vasculitis, multiple sclerosis, and tissue rejection associated with transplantation. Alemtuzumab destroys white blood cells that have a protein called CD52 on their surface and that might be among the cells attacking muscle.

Patients with s-IBM are eligible for this study. Candidates are screened with physical and neurological examinations, blood tests, and an electrocardiogram. Participants undergo the following tests and procedures:

- Campath administration: Patients are admitted to the NIH Clinical Center for 1 to 1-1/2 weeks for intravenous infusions of Campath, given every other day for a total of 4 infusions.

- Follow-up visits after infusions: Patients are monitored for up to 1 year with periodic blood tests, physical and neurological examinations, medical history, muscle strength measurements, and a review of symptoms, including the ability to perform daily living activities.

- Lymphapheresis: Patients undergo this procedure for collecting large numbers of white blood cells twice - once at the beginning of the study and again after 6 months. Blood is removed through a needle in an arm vein and flows through a machine that separates it into its components by centrifugation (spinning). The white cells and plasma are removed and the red cells and platelets are returned to the patients through the same needle or through another needle in the other arm.

- Muscle biopsy: Muscle biopsies are done in the operating room under local anesthetic. A small incision is made in the thigh or upper arm and a small piece of muscle is removed. Biopsies are done at the beginning of the study and again after 6 months.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Patients with confirmed diagnosis of s-IBM willing to undergo therapy with Alemtuzumab.

Willingness and legal ability to give and sign informed study consent.

Willingness to travel to the Clinical Center for planned studies and treatment as required by protocol.

Men and women of reproductive potential must agree to use an acceptable method of birth control during and for six months after completion of treatment.

Availability of tissue for testing. This will include muscle and peripheral blood lymphocytes isolated through routine lymphocytapheresis or phlebotomy.

EXCLUSION CRITERIA:

Immunosuppressive drug therapy at the time of or 6 months prior to enrollment. Specifically, candidates may not be taking Prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide methotrexate, or other agents whose concomitant use may enhance the toxicity of Alemtuzumab.

Any medical or personal difficulties that precludes serial follow-up visits.

Any active malignancy.

Significant coagulopathy or requirement for anticoagulation therapy that would contraindicate protocol.

Platelet count less than 100,000/mm(3).

Hemoglobin less than 9.0 mg/dl.

Any known immunodeficiency syndrome included HIV infection.

Any history of cardiac insufficiency, major vascular disease, or unstable coronary artery disease.

Any history of systemic or pulmonary edema.

Any history of previous treatment with monoclonal antibodies or sensitivity to the study drug (Alemtuzumab), pre-medication regimen, or prophylactic agents.

History of chronic hypotension (SBP less than 100 mmHg).

Any medical condition that would likely increase the risk of side effects of the study drug or confound the interpretation of the data including active infections.

Pregnancy and active nursing (breast feeding).

History of uncontrolled thyroid disease or a history of autoimmune thyroiditis.

Special Instructions: Currently Not Provided

Keywords:

Inflammation

Myositis

Humanized Monoclonal Antibody

Cytotoxic T Cells

Endomysial T Cells

Alemtuzumab

Monoclonal Antibodies

IBM

Anti-CD 52

Recruitment Keywords:

Inclusion Body Myositis

IBM

Conditions:

Myositis, Inclusion Body

Investigational Drug(s):

Alemtuzumab

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med. 1991 Nov 21;325(21):1487-98. PMID: 1658649

Dalakas MC, et al. Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology. 1997Mar;48(3):712-6. PMID: 9065553

Dalakas MC, et al. A controlled study of intravenous immunoglobulin combined with prednisone in the treatment ofIBM. Neurology. 2001 Feb 13;56(3):323-7. PMID: 11171896

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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