Anti-Interleukin-5 Antibody to Treat Hypereosinophilic Syndrome

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Brief Title

Anti-Interleukin-5 Antibody to Treat Hypereosinophilic Syndrome

Official Title

A Pilot Phase II Study of the Efficacy of Humanized Anti-IL5 Antibody (SCH55700) in Reducing Eosinophilia in Patients With Hypereosinophilic Syndrome or Eosinophilic Gastroenteritis Refractory to or Intolerant of Conventional Therapy

Brief Summary

      This study will examine the safety and effectiveness of a single dose of anti-interleukin-5
      antibody (SCH 55700) in reducing the number of eosinophils (a type of white blood cell) in
      patients with hypereosinophilic syndrome. Patients with this disease have too many
      eosinophils in the blood and in body tissues, which cause damage to the affected organs-most
      commonly the heart, nerves and skin. SCH 55700 is an antibody to interleukin 5-a hormone-like
      substance produced by white blood cells that plays a significant role in eosinophilia. SCH
      55700 has lowered eosinophilia blood counts in patients with asthma and reduced the number of
      these cells in tissues of animals with asthma.

      Patients with hypereosinophilic syndrome 18 years of age and older who have not responded to
      standard therapy with steroids, interferon and hydroxyurea or cannot take these drugs may be
      eligible for this study. Candidates will be screened with a medical history, physical
      examination, eye examination, and blood tests. Depending on the patient's symptoms, other
      diagnostic tests may be done, including studies of the eyes, lungs, skin, nerves or heart.
      Skin biopsy and bronchoalveolar lavage may be included in the diagnostic evaluation. For the
      skin biopsy, a small area about 1/3 inch in diameter is numbed and a small core of skin is
      surgically removed for study under the microscope. Bronchoalveolar lavage involves inserting
      a catheter (flexible tube) into the lungs to instill saline (salt water) and obtain a tissue
      sample. This test will be done only if clinically necessary.

      Those enrolled in the study will be admitted to the NIH Clinical Center for a single dose of
      SCH 55700, injected into an arm vein. They will be monitored in the hospital for at least 72
      hours for changes in eosinophil count and side effects of the injection. After discharge,
      laboratory tests will be done weekly for the first month, either at the Clinical Center or by
      the patient's local physician. Follow-up visits will then be scheduled monthly for 1 year or
      until the patient's eosinophil count returns to pre-treatment levels for 2 consecutive
      months. Follow-up visits will include a history, physical examination and blood tests,
      including studies on how immune cells and other substances in the blood activate or stimulate
      eosinophilia. A chest X-ray, electrocardiogram and pulmonary function tests will be done at
      1, 3, 6 and 12 months to evaluate organ damage. Other tests may be done if medically
      indicated.

      Bone marrow biopsy and aspiration will be done before receiving SCH 55700 and one month after
      the injection to evaluate the effects of SCH 55700 on eosinophil production in the bone
      marrow. For this test, an area of skin and bone is numbed and a very sharp needle is used to
      withdraw a sample of the bone marrow. Leukapheresis will also be done before and 1 month
      after SCH 55700 treatment to obtain cells for studying the effect of SCH 55700 on eosinophil
      activation, function and survival. For this procedure, whole blood is collected through a
      needle in an arm vein. The blood circulates through a machine that separates it into its
      components. The white cells are then removed, and the rest of the blood is returned to the
      body, either through the same needle used to draw the blood or through a second needle placed
      in the other arm.
    

Detailed Description

      The purpose of this study is to evaluate the efficacy of humanized monoclonal anti-IL5
      antibody, SCH 55700 in reducing peripheral blood eosinophilia in patients with either
      hypereosinophilic syndrome or eosinophilic gastroenteritis. Patients with hypereosinophilic
      syndrome refractory to or intolerant of therapy with conventional therapy (steroids,
      hydroxyurea and interferon alpha) will be admitted on this protocol. Additionally, subjects
      with eosinophilic gastroenteritis refractory or intolerant to conventional therapy (systemic
      glucocorticoids) will be admitted on this protocol. A thorough clinical evaluation will be
      performed with emphasis on potential sequelae of eosinophil-mediated tissue damage. A
      baseline bone marrow will be obtained to exclude neoplasia and to assess the degree and
      nature of eosinophilipoiesis. Blood cells and/or serum will also be collected to provide
      reagents (such as DNA, RNA, and specific antibodies) for use in the laboratory to address
      issues related to the immunologic basis of FHES and GE as well as their pathogenesis and
      treatment. Following intravenous administration of a single 1 mg/kg dose of the humanized
      monoclonal anti-IL5 antibody, SCH 55700, patients will be followed in an inpatient setting
      for a minimum of 72 hours for monitoring of adverse effects secondary to the infusion.
      Followup visits will be scheduled monthly for 1 year or until the peripheral eosinophil count
      returns to baseline. Patients showing a reduction in eosinophilia and evidence of clinical
      improvement will be eligible to receive 5 additional doses of 1 mg/kg of SCH 55700 at monthly
      intervals.
    

Study Phase

Phase 2

Study Type

Interventional




Condition

Hypereosinophilic Syndrome

Intervention

SCH55700


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

10

Start Date

June 2001

Completion Date

June 2003


Eligibility Criteria

        INCLUSION CRITERIA - HES:

        All subjects must meet the established diagnostic criteria for idiopathic hypereosinophilic
        syndrome: eosinophilia greater than 1,500/mm3 on two occasions at least 6 months apart, no
        known etiology for the eosinophilia despite careful clinical evaluation, evidence of end
        organ damage (histologic evidence of tissue infiltration by eosinophils and/or objective
        evidence of clinical pathology in any organ system that is temporarily associated with
        eosinophilia and not clearly attributable to another cause).

        All subjects must be at least 18 years of age.

        Failure of or contraindication to treatment with steroids, interferon alpha and hydroxyurea

        Negative serum beta-hCG within 24 hours of drug administration for women of childbearing
        potential must to exclude early pregnancy

        Agree to practice abstinence or effective contraception for 6 months following
        administration of the study drug

        INCLUSION CRITERIA - EG:

        All subjects must meet the established diagnostic criteria for eosinophilic
        gastroenteritis: gastrointestinal symptoms, histologic evidence of gastrointestinal tissue
        infiltration by eosinophils with greater than or equal to 25 eosinophils per high powered
        field, no known etiology for the eosinophilia despite careful clinical evaluation

        Eosinophilia greater than 860/mm3 on two occasions at least 6 months apart

        Evidence of hypersensitivity to foods or aeroallergens as determined by skin or RAST
        testing

        All subjects must be at least 18 years of age.

        Failure of or contraindication to treatment with steroids.

        Negative serum beta-hCG within 24 hours of drug administration for women of childbearing
        potential must to exclude early pregnancy

        Agree to practice abstinence or effective contraception for 6 months following
        administration of the study drug

        EXCLUSION CRITERIA - HES and GE:

        Pregnant or nursing women

        HIV positivity or other known immunodeficiency

        Use of any other investigational agent within 30 days of the study

        Any condition that, in the investigator's opinion, places the patient at undue risk by
        participating in the study.
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00017862

Organization ID

010155

Secondary IDs

01-I-0155


Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

, , 


Verification Date

June 2003