Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00044304
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2002-08-24
Brief Title:
Tyrosine Kinase Inhibition to Treat Myeloid Hypereosinophilic Syndrome
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Efficacy of Tyrosine Kinase Inhibition in Reducing Eosinophilia in Patients With Myeloid andor Steroid-Refractory Hypereosinophilic Syndrome
Status:
RECRUITING
Status Verified Date:
2024-10-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 andor 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
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
Detailed Description:
This study will evaluate the safety and effectiveness of imatinib mesylate in reducing the number of eosinophils a type of white blood cell in patients with hypereosinophilic syndrome HES Patients with HES have elevated counts of eosinophils in the blood and body tissues which can cause damage to these tissues Although HES can involve any tissues the heart nerves and skin are most often affected Several drugs including steroids interferon and hydroxyurea can lower eosinophil counts however these drugs have drawbacks in that they do not work in all patients with HES or they may work only temporarily or patients may develop side effects that require stopping the drugs Imatinib mesylate is a new drug approved to treat gastrointestinal tumors and chronic myelogenous leukemia Some data suggest that imatinib mesylate may be useful in treating a subgroup of patients with HES
Patients with HES who are 18 years of age and older may be eligible for this study Candidates will be screened with a medical history physical examination blood tests electrocardiogram EKG echocardiogram ultrasound examination of the heart pulmonary lung function tests eye exam and a bone marrow examination to determine if they fall into the subgroup of patients likely to respond to this therapy For the bone marrow procedure an area of skin and bone is numbed and a very sharp needle is inserted into the bone to draw out a sample of bone marrow for evaluation under the microscope
Patients enrolled in the study will take imatinib mesylate daily Any other drugs they may be taking for HES as well as other drugs they are taking that may interact with imatinib mesylate will be tapered and stopped If it is not possible to stop taking certain drugs for other conditions their dosages may be adjusted Patients will be monitored weekly with laboratory testing during the first month of treatment and whenever neutrophil counts drop below 1500mm3 or platelets fall below 100000mm3 If blood counts remain high enough monitoring will be reduced to every 2 weeks for 3 months and once a month after that Patients will have a clinic visit at NIH 1 month after beginning the drug for a clinical and laboratory evaluation including a repeat bone marrow examination Patients whose eosinophil counts are not lowered after 4 weeks of treatment will leave the study Those who respond to therapy will return to NIH every 3 months for a history and physical examination laboratory tests EKG echocardiogram and pulmonary function testing to determine how treatment is affecting disease progression In some participants with stable disease where an optimal dose of imatinib mesylate has been identified visits may be extended to every six months In addition the following procedures will be done solely for research purposes
Blood tests to determine the effects of imatinib mesylate on immune cells including eosinophils
Leukapheresis to study the effects of imatinib mesylate on eosinophils For this procedure whole blood is collected through a needle in an arm vein similar to donating blood The blood circulates through a machine that separates it into its components and the white cells are removed The rest of the blood is returned to the body either through the same needle or through another needle in the other arm
Bone marrow examinations will be done during the screening tests and again 1 month after starting treatment to look at newly developing cells in the bone marrow
Genetic testing to determine how imatinib mesylate is able to lower eosinophil counts in patients with HES
Patients with HES who are 18 years of age and older may be eligible for this study Candidates will be screened with a medical history physical examination blood tests electrocardiogram EKG echocardiogram ultrasound examination of the heart pulmonary lung function tests eye exam and a bone marrow examination to determine if they fall into the subgroup of patients likely to respond to this therapy For the bone marrow procedure an area of skin and bone is numbed and a very sharp needle is inserted into the bone to draw out a sample of bone marrow for evaluation under the microscope
Patients enrolled in the study will take imatinib mesylate daily Any other drugs they may be taking for HES as well as other drugs they are taking that may interact with imatinib mesylate will be tapered and stopped If it is not possible to stop taking certain drugs for other conditions their dosages may be adjusted Patients will be monitored weekly with laboratory testing during the first month of treatment and whenever neutrophil counts drop below 1500mm3 or platelets fall below 100000mm3 If blood counts remain high enough monitoring will be reduced to every 2 weeks for 3 months and once a month after that Patients will have a clinic visit at NIH 1 month after beginning the drug for a clinical and laboratory evaluation including a repeat bone marrow examination Patients whose eosinophil counts are not lowered after 4 weeks of treatment will leave the study Those who respond to therapy will return to NIH every 3 months for a history and physical examination laboratory tests EKG echocardiogram and pulmonary function testing to determine how treatment is affecting disease progression In some participants with stable disease where an optimal dose of imatinib mesylate has been identified visits may be extended to every six months In addition the following procedures will be done solely for research purposes
Blood tests to determine the effects of imatinib mesylate on immune cells including eosinophils
Leukapheresis to study the effects of imatinib mesylate on eosinophils For this procedure whole blood is collected through a needle in an arm vein similar to donating blood The blood circulates through a machine that separates it into its components and the white cells are removed The rest of the blood is returned to the body either through the same needle or through another needle in the other arm
Bone marrow examinations will be done during the screening tests and again 1 month after starting treatment to look at newly developing cells in the bone marrow
Genetic testing to determine how imatinib mesylate is able to lower eosinophil counts in patients with HES
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-I-0286 | None | None | None |