Tyrosine Kinase Inhibition to Treat Myeloid Hypereosinophilic Syndrome

Running, not enrolling · Phase 2

Conditions studied: Eosinophilic Myeloid Neoplasm, Hypereosinophilic Syndrome

In brief

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. ...

Key facts

Study ID

NCT00044304

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

70

Starts

2002-09-26

Expected to finish

2027-03-10

Last updated by the study team

2026-03-16

Who can join

Age: 2 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnant or nursing women.*
• D816V KIT-positive systemic mastocytosis
• Uncontrolled HIV infection (absolute lymphocyte count <200/mm\^3 and/or HIV RNA level >500 copies/ml)
• ANC <1000/mm\^3 or platelet count <10,000/mm\^3 or <50,000/m\^3 with clinical evidence of bleeding.
• Elevated transaminases (>5 times the upper limit of normal) or elevated bilirubin (>3 times the upper limit of normal).
• Any condition that, in the investigator s opinion, places the patient at undue risk by participating in the study.
• An individual who meets any of the following criteria will be excluded from participation in the ruxolitinib treatment arm of this study:
• Evidence of B-cell clonality by PCR or flow cytometry.
• Active tuberculosis, or acute or chronic active infection with hepatitis B or C*.
• Treatment with fluconazole >200 mg daily.
• Participants with active tuberculosis will be excluded. The most current Infectious Diseases Society of America guidelines will be followed regarding isoniazid therapy for latent tuberculosis. Participants who refuse recommended prophylactic therapy for tuberculosis will be counseled regarding the risks of reactivation of tuberculosis during ruxolitinib therapy but will not be systematically excluded. Molecular and serologic tests for hepatitis B and serology for hepatitis C will be performed regardless of vaccination history. Participants with evidence of active or chronic infection with hepatitis B or positive hepatitis C serology will be excluded from participation in the ruxolitinib arm of the protocol. Specifically, a positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B anti-surface antibody-positive and hepatitis B anti-core antibody-negative) or a fully resolved acute hepatitis B infection is not an exclusion criterion. Patients with an indolent chronic hepatitis B infection (normal alanine aminotransferase [ALT], aspartate aminotransferase [AST], and albumin, and no radiographic or biopsy evidence of cirrhosis) will be evaluated by an NIH hepatologist and may be eligible. Patients who choose to remain on study with evidence of prior hepatitis B infection will be counseled regarding the risks of reactivation prior to initiation of ruxolitinib therapy.

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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