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

Condition(s) targeted: Myelofibrosis; Myeloid Metaplasia; Agnogenic Myeloid Metaplasia; Chronic Myelomonocytic Leukemia

Intervention: Imatinib mesylate (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Dana-Farber Cancer Institute

Official(s) and/or principal investigator(s):
Daniel J. DeAngelo, MD, PhD, Principal Investigator, Affiliation: Dana-Farber Cancer Institute

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.

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 design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome: 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

Secondary outcome:

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

to determine the biologic activity of Gleevec in patients with BCR-negative myeloproliferative disorders including myelofibrosis with myeloid metaplasia or 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

Massachusetts General Hospital, Boston, Massachusetts 02115, United States

Starting date: May 2002
Ending date: August 2008
Last updated: December 20, 2007