A Study of Gleevec in Patients With Idiopathic Myelofibrosis or Chronic Myelomonocytic Leukemia (CMML)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effects (good and bad) of Gleevec in patients with BCR-negative myeloproliferative disorders including myelofibrosis with myeloid metaplasia and chronic myelomonocytic leukemia.

Detailed Description
-----------------
Gleevec will be administered at a dose of 400 mg orally once daily. Patients will continue to receive the drug until either drug progression or the development of intolerable side effects. Patients will be assessed with a complete blood count weekly for the first 8 weeks and will have monthly physical examinations and bone marrow examinations every 3 months.

Official Title
-----------------
A Phase II Study of Gleevec (Imatinib Mesylate) In Patients With BCR-Negative Myeloproliferative Disorders Including Patients With Idiopathic Myelofibrosis With Myeloid Dysplasia or Chronic Myelomonocytic Leukemia

Conditions
-----------------
Myelofibrosis, Myeloid Metaplasia, Agnogenic Myeloid Metaplasia, Chronic Myelomonocytic Leukemia

Intervention / Treatment
-----------------
* Drug: Imatinib mesylate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must have a clinical diagnosis of myelofibrosis with myeloid metaplasia or chronic myelomonocytic leukemia (CMML). Patients may be entered based on a prior cytogenetic karyotype showing the absence of the Philadelphia chromosome. Patients may be entered prior to completion of reverse transcription-polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH) studies, but a patient who is subsequently found to be BCR-ABL or FISH positive will be removed from protocol treatment. FISH will only be performed on patients with a normal karyotype. A PCR sample will be sent on all patients. The patients with myelodysplasia must have French-American-British (FAB) subtype chronic myelomonocytic leukemia (CMML) defined as peripheral blood monocytosis, and less than 30 percent blasts in the peripheral blood or the bone marrow. The patients with myelofibrosis with myeloid metaplasia can have one of the following: agnogenic myeloid metaplasia (idiopathic myelofibrosis), or post-polycythemic myeloid metaplasia (post-polycythemic myelofibrosis), or post-thrombocythemic myeloid metaplasia. Estimated life expectancy of 6 months or greater. Serum bilirubin equal to or less than twice the upper limit of normal. Serum SGOT and SGPT equal to or less than twice the upper limit of normal. Serum creatinine equal to or less than twice the upper limit of normal. Age at least 18 years. Greater than 4 weeks from any chemotherapy (except hydroxyurea), radiotherapy, immunotherapy, or systemic glucocorticoid therapy (non-glucocorticoid hormonal therapy is allowed). Systemic glucocorticoid therapy for non-malignant disease is allowed. The last dose of hydroxyurea must be 24 hours prior to the initiation of Gleevec. Greater than 2 months following bone marrow or peripheral blood stem cell transplantation or treatment with donor lymphocyte infusion (DLI). Exclusion Criteria: Uncontrolled active infection. Pregnancy or nursing mothers. Patients with myelofibrosis with myeloid metaplasia or chronic myelomonocytic leukemia who have transformed to acute myelogenous leukemia. Prior treatment or diagnosis of acute myelogenous leukemia. Patients with Philadelphia positive cytogenetics by either peripheral blood or bone marrow sampling. Eastern Cooperative Oncology Group (ECOG) performance status > 3. Prior exposure to Gleevec. Active central nervous system (CNS) disease. Evidence of infection with the human immunodeficiency virus. Active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mono-Therapy Gleevec<br>Gleevec administered orally at a pre-determined dose once daily. | Drug: Imatinib mesylate<br>* 400mg orally once daily until disease progression or unacceptable side effects<br>* Other names: Gleevec;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the overall response rate of Gleevec as a single agent in patients with BCR-negative myeloproliferative disorders including myelofibrosis with myeloid metaplasia and chronic myelomonocytic leukemia |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety and efficacy of Gleevec as a single agent in patients with BCR-negative myeloproliferative disorders including myelofibrosis with myeloid metaplasia or chronic myelomonocytic leukemia |  | 3 years | 
| to determine the biologic activity of Gleevec in patients with BCR-negative myeloproliferative disorders including myelofibrosis with myeloid metaplasia or chronic myelomonocytic leukemia |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
myelofibrosis, agnogenic myeloid metaplasia with myelofibrosis, CMML, chronic myelomonocytic leukemia, imatinib mesylate, Gleevec