Steroid Treatment for Hypereosinophilic Syndrome

Related Clinical Trial
MAP to Provide Access to Nilotinib, for Patients With HES Eosinophilia Diagnosis A Multi-center, Open-label Extension, Safety Study of Mepolizumab in Subjects With Hypereosinophilic Syndrome (HES) From Study 200622 This Record Contains Information About the Mepolizumab Compassionate Use (CU) Product Activities: 104317: CU and Long-Term Access Study of Mepolizumab in HES. 201956:A Long-term Access Programme for Subjects With Severe Asthma 112562: Expanded Access for Patients With Hypereosinophilic Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes Study to Evaluate Safety and Efficacy of Benralizumab in Subjects With Hypereosinophilic Syndrome Anti-Interleukin-5 (IL-5) Study for Hypereosinophilic Syndrome A Longitudinal Study of Familial Hypereosinophilia (FE): Natural History and Markers of Disease Progression Phase II Gleevec Idiopathic Hypereosinophilic Syndrome Anti-Interleukin-5 Antibody to Treat Hypereosinophilic Syndrome Intravenous Mepolizumab In Subjects With Hypereosinophilic Syndromes (HES) Study to Evaluate Safety and Efficacy of Dexpramipexole (KNS-760704) in Subjects With Hypereosinophilic Syndrome Tyrosine Kinase Inhibition to Treat Myeloid Hypereosinophilic Syndrome Steroid Treatment for Hypereosinophilic Syndrome Natural History of Hypereosinophilia and Hypereosinophilic Syndromes A Study to Determine the Safety and Efficacy of Imatinib Mesylate in Patients With Idiopathic Hypereosinophilic Syndrome Identification of New Markers in the Hypereosinophilic Syndrome A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) Open-Label Extension Of Intravenous Mepolizumab In Patients With Hypereosinophilic Syndrome

Brief Title

Steroid Treatment for Hypereosinophilic Syndrome

Official Title

Assessment of Glucocorticoid Responsiveness and Mechanisms of Resistance in Hypereosinophilic Syndromes

Brief Summary

      Background:

      - Hypereosinophilic syndrome (HES) is a disorder in which the body has too many eosinophils
      (a type of white blood cell). Too many eosinophils in HES can cause damage to the heart,
      nerves, or skin. Certain drugs can help lower eosinophil counts to prevent tissue damage.
      Corticosteroids, such as prednisone, are used for initial therapy in this disorder. Although
      most people respond to prednisone, some people develop side effects from it, or do not
      respond very well to treatment. Better ways of determining the dose to give could help to
      decide on the best therapy for HES.

      Objectives:

        -  To determine whether a single-dose of prednisone can be used to predict which people
           with hypereosinophilia respond to treatment.

        -  To study lack of response to steroid treatment in people with HES.

      Eligibility:

      Inclusion criteria:

        -  Individuals with hypereosinophilic syndrome with high eosinophil counts.

        -  Individuals who are willing to have blood drawn before and after getting steroids.

      Exclusion criteria:

        -  Individuals who are on more than 10mg of prednisone (or similar drug)

        -  Individuals with hypereosinophilic syndrome who are on other medications that could
           interfere with the study

        -  Women who are pregnant or breast-feeding

        -  Individuals who have a known gene mutation associated with chronic eosinophilic leukemia

        -  Children less than 18 years old who weigh less than 48kg or 106lb

      Design:

        -  Participants will have a screening visit with a physical exam and medical history. Blood
           and urine samples will be collected.

        -  Participants will have a single dose of the steroid prednisone by mouth in the morning.
           Blood samples will be collected 2, 4, 24 hours after this dose.

        -  On the day after the steroid dose, participants will provide another blood sample in the
           morning.

        -  Participants will start to take prednisone daily when they return home. Blood samples
           will be collected weekly at the participant s doctor s office. The dose of prednisone
           will be lowered depending on the weekly eosinophil count. We will try to get each person
           on the lowest dose of prednisone possible that will control the disorder. Participants
           who do not respond or have severe side effects will be taken off prednisone. Other
           treatments will be considered for people who do not respond to steroids. The goal is to
           evaluate the response to prednisone. Our research will try to figure out why some people
           do not respond to steroids. Most people will complete the study within 6 to 16 weeks,
           depending on their response to prednisone.
    

Detailed Description

      This study aims to develop a model to determine whether a single, oral, weight-based dose of
      glucocorticoid (GC) can predict clinical and biologic response to GC s over the long term in
      subjects with hypereosinophilic syndrome (HES). Subjects with FIP1L1/PDGFRA-negative HES, who
      are symptomatic with eosinophil count >1500/microL and receiving less than or equal to10 mg
      prednisone daily, will be enrolled. A single oral dose of prednisone (1 mg/kg rounded to the
      nearest 5mg) will be administered. Eosinophil count and various laboratory parameters will be
      assessed at 2 hours, 4 hours and 24 hours following prednisone administration (investigators
      will be blinded to the results of the eosinophil counts). The subjects will then begin GC
      therapy at 30 mg prednisone daily followed by a standardized taper. The lowest dose of GC at
      which symptoms and eosinophilia are controlled will be compared to the change in eosinophil
      count at 2, 4 and 24 hours post-challenge. Mechanisms and in vitro correlates of GC
      resistance will also be explored.
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

To develop a model to determine whether a single dose steroid challenge can be used to predict GC responsiveness in subjects with HES.


Condition

Eosinophilia

Intervention

prednisone

Study Arms / Comparison Groups

 1
Description:  All subjects will receive a single oral dose of prednison (1 mg/kg rounded to the neares 5 mg). The subjects will then begin GC therapy at 30 mg prednisone daily followed by a standardized taper.

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

100

Start Date

February 16, 2012

Completion Date

December 31, 2024

Primary Completion Date

December 31, 2024

Eligibility Criteria

        -  SUBJECT INCLUSION CRITERIA:

        Subjects on Protocol #94-I-0079 will be eligible for participation in the study only if all
        of the following criteria apply:

          1. Subject meets diagnostic criteria for HES (AEC >1500/microL, absence of a secondary
             cause and signs and/or symptoms attributable to the eosinophilia)

          2. Willingness to perform the timed steroid challenge

          3. Appropriate candidate for GC treatment after challenge

          4. Willingness to have samples stored for future research

        SUBJECT EXCLUSION CRITERIA:

        A subject will not be eligible to participate in the study if any of the following apply:

          1. Receiving >10 mg prednisone or equivalent at the time of enrollment.

          2. Receiving less than or equal to 10 mg of prednisone or equivalent but have not been on
             a fixed dose for at least 3 weeks (subjects on a current corticosteroid taper will be
             excluded).

          3. AEC less than or equal to 1500/microl at the time of enrollment.

          4. Use of immunomodulatory medications, (other than less than or equal to 10 mg/day
             prednisone) including but not limited to biologics, within the past 6 months.

          5. Pregnant at the time of evaluation.

          6. Have a known mutation in the FIP1L1-PDGFR gene.

          7. Any condition that, in the opinion of the investigator, places the subject at undue
             risk by participating in the protocol.

          8. Weight less than 48 kg (106 lbs) in subjects less than 18 years of age.
      

Gender

All

Ages

7 Years - 100 Years

Accepts Healthy Volunteers

No

Contacts

Paneez Khoury, M.D., (301) 402-5969, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01524536

Organization ID

120026

Secondary IDs

12-I-0026

Responsible Party

Sponsor

Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

Paneez Khoury, M.D., Principal Investigator, National Institute of Allergy and Infectious Diseases (NIAID)


Verification Date

March 13, 2020