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
- 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
- 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.
Sporadic Inclusion-Body Myositis (s-IBM) is the most common muscle disease in patients above
the age of 50 years. It is an inflammatory myopathy mediated by sensitized, cytotoxic CD8+
T cells that clonally expand in situ and invade MHC-I-expressing muscle fibers. The antigen
recognized by the T cells is unknown. The disease is progressive, resists the currently
available immunotherapies and leads to wheelchair confinement. Applying therapeutic
strategies with agents that deplete T cells clones and investigating the antigenic
specificity of the endomysial T cells is expected to enhance our understanding of the cause
of s-IBM and lead to clinical improvement. The present study is designed to: a) test in a
pilot study the safety, T cell depletion of the endomysial T cells and clinical efficacy of
the monoclonal antibody Alemtuzumab in 20 patients with s-IBM followed for 12 months by
serial quantitative assessment of muscle strength; b) explore the spectrum of the antigens
recognized by the T cells extracted from the muscle biopsy specimens by searching for immune
dominant peptides using positional scanning synthetic combinational peptide libraries,
before and after therapy; and c) determine the reciprocal relationship between clinical
response and endomysial inflammatory mediators before and after treatment. It is
anticipated that the study may lead to identification of putative antigens that trigger the
disease, clarify the significance of the inflammation and amyloid deposits in muscle fiber
injury and provide a novel therapy for s-IBM patients.
- Only patients who are currently enrolled in protocol 02-N-0121 Study of Immune
Dysregulation in Patients with Sporadic Inclusion Body Myositis (s-IBM) will be
considered for enrollment in protocol 04-N-0133.
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
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.
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
Any medical or personal difficulties that precludes serial follow-up visits.
Any active malignancy.
Significant coagulopathy or requirement for anticoagulation therapy that would
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
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.