Steroid Treatment for Hypereosinophilic Syndrome

Assessment of Glucocorticoid Responsiveness and Mechanisms of Resistance in Hypereosinophilic Syndromes

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01524536

Enrollment

Registered

2012-02-02

Start date

2012-02-16

Completion date

2020-12-10

Last updated

2022-02-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Eosinophilia, Hematologic Diseases, Hypereosinophilic Syndrome, Leukocyte Disorder

Keywords

Hypereosinophilia, Hypereosinophilic Syndrome, Corticosteroids, Therapy, HES

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/PDGFRalpha-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.

Interventions

DRUGprednisone

Glucocorticoids (GC) are considered the first- line therapy for hypereosinophilic syndrome.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

7 Years to 100 Years

Healthy volunteers

Inclusion 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. Subjects must be 7 years of age or older to enroll 2. Subject meets diagnostic criteria for HES (AEC \>1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia) 3. AEC greater than 1500 microL obtained within 14 days prior to enrollment 4. Willingness to perform the timed steroid challenge 5. Appropriate candidate for GC treatment after challenge 6. 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 on the day of the steroid challenge 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 screening. 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.

Design outcomes

Primary

Measure	Time frame	Description
Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge	24 hours	Response to glucocorticoid challenge as assessed by the percentage of the eosinophil count 24 hours post-glucocorticoid challenge relative to the Baseline AEC for each participant. Measure Description (%): Percent of baseline AEC is defined as the Absolute Eosinophil Count at 24 hours divided by the Absolute Eosinophil Count at Baseline \*100.

Secondary

Measure	Time frame	Description
Participants With Glucocorticoid Responsiveness - LHES Variant	Baseline (Day 1)	Participants with lymphoid hypereosinophilic syndromes (LHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Participants With Glucocorticoid Responsiveness - MHES Variant	Baseline (Day 1)	Participants with myeloid hypereosinophilic syndromes (MHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Participants With Glucocorticoid Responsiveness - Overlap HES Subtypes	Baseline (Day 1)	Participants with overlap hypereosinophilic syndromes that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Participants With Glucocorticoid Responsiveness - IHES Variant	Baseline (Day 1)	Participants with idiopathic hypereosinophilic syndromes (IHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Mean Baseline Absolute Eosinophil Count	Baseline (Day 1)	Mean baseline absolute eosinophil count in participants prior to initiation of glucocorticoids
Participants With Glucocorticoid Responsiveness - Cardiac Involvement	Baseline (Day 1)	Cardiac involvement in participants with hypereosinophilic syndromes (HES)
Participants With Glucocorticoid Responsiveness - Pulmonary Involvement	Baseline (Day 1)	Pulmonary involvement in participants with hypereosinophilic syndromes (HES)
Mean Baseline IgE Level	Baseline (Day 1)	Mean baseline immunoglobulin E (IgE) level in participants prior to initiation of glucocorticoid

Countries

United States

Participant flow

Pre-assignment details

26 participants were consented to protocol but three did not meet the eligibility criteria so did not start study.

Participants by arm

Arm	Count
Steroid Challenge A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.	23
Total	23

Baseline characteristics

Characteristic	Steroid Challenge
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	1 Participants
Age, Categorical Between 18 and 65 years	22 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants
Race (NIH/OMB) White	15 Participants
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	11 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 23
other Total, other adverse events	7 / 23
serious Total, serious adverse events	0 / 23

Outcome results

Primary

Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge

Response to glucocorticoid challenge as assessed by the percentage of the eosinophil count 24 hours post-glucocorticoid challenge relative to the Baseline AEC for each participant. Measure Description (%): Percent of baseline AEC is defined as the Absolute Eosinophil Count at 24 hours divided by the Absolute Eosinophil Count at Baseline \*100.

Time frame: 24 hours

Population: All participants who received the single challenge dose of prednisone

Arm	Measure	Value (MEAN)
Steroid Challenge - Responders	Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge	-69.6 percentage of eosinophil count
Steroid Challenge - Non-responders	Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge	-13.6 percentage of eosinophil count

Secondary