Clinical trial NCT00136409: A Study of Gleevec in Patients With Idiopathic Myelofibrosis or Chronic Myelomonocytic Leukemia (CMML)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelofibrosis
Myeloid Metaplasia
Agnogenic Myeloid Metaplasia
Chronic Myelomonocytic Leukemia
Keywords: myelofibrosis
agnogenic myeloid metaplasia with myelofibrosis
CMML
chronic myelomonocytic leukemia
imatinib mesylate
Gleevec
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: Novartis
First posted: 2005-08-29
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: 3 years
Secondary outcomes:
measure: 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
timeFrame: 3 years
measure: to determine the biologic activity of Gleevec in patients with BCR-negative myeloproliferative disorders including myelofibrosis with myeloid metaplasia or chronic myelomonocytic leukemia
timeFrame: 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Daniel J. DeAngelo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: