Tyrosine Kinase Inhibition to Treat Myeloid Hypereosinophilic Syndrome
Status:
Recruiting
Trial end date:
2026-01-01
Target enrollment:
Participant gender:
Summary
The purpose of this study is to evaluate the safety and efficacy of the tyrosine kinase
inhibitor, imatinib mesylate (Gleevec ) in reducing peripheral blood eosinophilia in patients
with the myeloid form of hypereosinophilic syndrome (HES). Patients with the
hypereosinophilic syndrome who meet a set of criteria designed to select patients with the
myeloid form of the disease, as well as patients without myeloid disease who are refractory
to standard therapy for HES, 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 leukemia or lymphoma and to
assess the degree and nature of eosinophilopoiesis. Bone marrow, blood cells and/or serum
will also be collected to test for the presence of a recently described mutation that is
associated with imatinib-responsiveness in HES, and to provide reagents (such as DNA, RNA,
and specific antibodies) and for use in the laboratory to address issues related to the
mechanism of action of imatinib mesylate in HES. Imatinib mesylate will be initiated at a
dose of 400 mg daily, the FDA-approved dose for the treatment of chronic myelogenous
leukemia. In patients who demonstrate a complete clinical and hematologic response to
imatinib therapy and who do not have life-threatening disease, the dose will be decreased
gradually to 100mg daily and then discontinued. In order to minimize bone marrow suppression,
other myelosuppressive agents will be tapered and discontinued during the first week of
therapy with imatinib mesylate. Complete blood counts will be performed weekly for the first
month and biweekly thereafter. Clinical assessments will be performed every three months to
assess progression of end organ damage.
In patients who demonstrate a complete clinical and hematologic response to imatinib therapy
and who do not have life-threatening disease, the dose will be decreased gradually to 100 mg
daily and then discontinued. In the event of clinical, hematologic or molecular relapse
during the taper, the imatinib dose will be increased to a maximum of 600 mg daily to achieve
a second remission. Laboratory monitoring will be performed as above except for molecular
monitoring which will be monitored monthly if drug is discontinued or molecular relapse
occurs. Once a stable dosing regimen is achieved for greater than or equal to 6 months in
subjects who have undergone dose descalation or greater than or equal to 2 years in subjects
receiving 300-400 mg of imatinib daily who did not qualify for dose de-escalation, the
frequency of NIH visits and end organ assessments will be decreased to 6 months, with
molecular monitoring every 3 months and monthly routine laboratory assessments.
...
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)