Tyrosine Kinase Inhibition to Treat Myeloid Hypereosinophilic Syndrome

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Study ID
NCT00044304
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Eosinophilic Myeloid Neoplasm
  • Hypereosinophilic Syndrome

Eligibility Criteria

Sex
ALL
Age
2 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Imatinib — DRUG
    The dosing regimen to be used initially (400 mg po qd in adults and 260 mg/m2/day in children with food and a glass of water) is identical to that recommended by the FDA for the treatment of the chronic phase of chronic myelogenous leukemia (CML) (Prod Info Gleevec ). In patients with ANC \<1500/mm3, platelet counts \< 75,000mm3 or abnormal liver function tests (ALT or AST \> 2.5 or bilirubin \> 3 times the upper limit of normal), the starting dose will be reduced to 300 mg po qD.
  • Ruxolitinib — DRUG
    The dosing regimen to be used initially (15 mg po bid) is identical to that recommended by the FDA for the treatment of myelofibrosis with platelet counts of 100-200,000/mm3 (Prod Info ruxolitinib). In patients with platelet counts \<100,000/mm3, moderate renal impairment (CrCl \<60 mL/min) or abnormal liver function tests (ALT or AST \> 2.5 or bilirubin \> 3 times the upper limit of normal), the starting dose will be reduced to 10 mg bid. The recommended guidelines for dose adjustment during therapy and discontinuation of therapy in myelofibrosis will be followed.

Study Details

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 Dates

Start date
Sep 26, 2002
Status verified
Mar 2026
Primary completion
Nov 16, 2023
Completion
Mar 10, 2027

Study Design

Enrollment
70 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Imatinib
    open label imatinib mesylate treatment
  • Experimental: Ruxolitinib
    open label ruxolitinib treatment

Primary Outcome Measure

peripheral blood absolute eosinophil count. [ Time Frame: one month (for imatinib) and 3 months (for ruxolitinib). ]

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892-

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