This study will evaluate the effectiveness of the drug daclizumab for treating patients with
chronic immune thrombocytopenia (ITP), a disease in which the immune system destroys
platelets (blood cells involved in the clotting process). Patients with ITP have abnormal
bruising and bleeding; severe disease can be life-threatening. For many patients, standard
drug treatments are not effective, and many of the drugs used may have significant side
effects with long-term use. Daclizumab is a genetically engineered antibody that suppresses
the immune system and has been used primarily to prevent rejection in patients who have had
organ transplants. Daclizumab has fewer side effects than other immune suppressant drugs.
Patients with ITP 18 years of age or older who have platelet counts less than
30,000/microliter and have not responded to prednisone treatment may be eligible for this
study. Candidates will be screened with a medical history, physical examination, and blood
Participants will have a 15-minute infusion of daclizumab every 2 weeks for five doses.
They will be seen by a physician at least once every 2 weeks while receiving the drug and
then at weeks 12, 20, and 32 of the study. Blood will be drawn at the 4- and 8-week visits
during treatment for diagnostic tests, and at each follow-up visit after treatment to assess
the response to therapy.
Patients who respond well to treatment will have their pre-study immunosuppressive medicines
tapered gradually one at a time starting with the 1-month follow-up visit. If their
platelet count falls to pre-treatment levels at any time during the tapering, the dose
reduction will stop and pre-study medications will be re-started, if necessary.
Immune thrombocytopenia (ITP) is an acquired blood disease in which the individual's immune
system destroys platelets, the blood cells responsible for clotting. A number of standard
treatments exist to decrease the destruction of platelets, including drugs such as the
steroid hormone prednisone, or removal of the spleen. Over a third of adult patients will
not maintain adequate platelet counts with these treatments. Alternative treatments may be
indicated due to bleeding symptoms or baseline platelet counts less than 20,000/ul, a level
at which spontaneous serious bleeding can occur. Therapy for chronic ITP is generally
effective in less than 30-50% of patients, however, and most of these agents have
significant toxicities with long-term use, are expensive, or their administration interferes
with daily activities.
Daclizumab is a humanized anti-interleukin-2 receptor monoclonal antibody that works by
targeting and impairing activated T lymphocytes, a subset of white blood cells that has been
thought to be involved in the development and maintenance of ITP. Daclizumab is a
well-tolerated and time-limited therapy, and is easily administered on an outpatient basis.
The purpose of this study is to test the efficacy of daclizumab as either a sole agent in
the treatment of chronic, symptomatic ITP, or as a treatment that might allow a decrease or
discontinuation of medications such as prednisone.
Male or female greater than or equal to 18 years old
Immune thrombocytopenia, and all of the following:
at least three months since initial diagnosis
lack of sustained response to initial treatment with prednisone, characterized by failure
to maintain a platelet count of at least 30,000/ul for at least six weeks using prednisone
at a dose of at least 10 mg per day
baseline platelet count (as determined by an average of platelet count values over two
months immediately prior to study entry) of less than 30,000/ul
*Note: In patients receiving IVIG or anti-D, platelet values immediately prior to
infusion of the drug (i.e., at platelet nadir) will be considered in the determination of
the baseline platelet value.
Splenectomy or prior use of second-line immunomodulatory treatments (such as, but not
limited to, CSA, danazol, azathioprine or cyclophosphamide) will not be considered a
requirement for inclusion.
ECOG performance status greater than 1
Concurrent symptomatic autoimmune hemolysis (Evans syndrome) characterized by hemoglobin
less than 10 gm/dl or requirement for more than two units red cells within three months of
enrollment, due to hemolysis
Concurrent autoimmune disorders requiring treatment for involvement of organ systems other
Initiation of any new immunomodulator agent, or increase in dose or frequency of any
existing immunomodulator agent (such as, but not limited to, CSA, danazol, azathioprine or
cyclophosphamide; IVIG and anti-D excepted) within two months of study entry
Autologous transplantation for immune thrombocytopenia within one year of study entry
Concurrent bleeding diathesis
Echinacea use within three months of study entry
Pregnancy or lactation
Chronic or current clinically significant infection, including HIV positivity and acute or
persistent hepatitis B and C virus infection (characterized by elevated transaminases and
positive hepatitis B surface antigen [HBsAg], or anti-hepatitis C virus [anti-HCV]
History of active M. Tuberculosis infection
Diagnosis of malignancy (with the exception of non-melanoma skin cancer and other
malignancies which by virtue of surgical resection and no recurrence for at least five
years prior to enrollment are considered to be cured)
Inadequate mental capacity to give informed consent