Clinical trial NCT00245128: Imatinib Mesylate in Treating Patients With Myelofibrosis
Official title: A Phase II Pilot Study to Determine the Safety and Preliminary Efficacy of Imatinib Mesylate (Gleevec) in Patients With Myelofibrosis With Myeloid Metaplasia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Myeloproliferative Disorders
Keywords: chronic idiopathic myelofibrosis
polycythemia vera
essential thrombocythemia
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-10-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects of imatinib mesylate and how well it works in treating patients with myelofibrosis.

Detailed description: OBJECTIVES:

Primary

* Determine the safety, efficacy, and tolerability of imatinib mesylate in patients with myelofibrosis with myeloid metaplasia.
* Determine the 3-, 6-, and 12-month major and minor erythroid response rates in patients treated with this drug.

Secondary

* Determine reduction in marrow fibrosis in patients treated with this drug.
* Determine decrease in spleen size in patients treated with this drug.

OUTLINE: This is a multicenter, open-label, nonrandomized, pilot study.

Patients receive oral imatinib mesylate once daily for 1 year in the absence of disease progression or unacceptable toxicity. Patients who do not experience a minor erythroid response or a 50% reduction in spleen size after 6 months of treatment are removed from the study. Patients experiencing clinical benefit (e.g., ongoing erythroid response) after 1 year of treatment may continue treatment with imatinib mesylate as above at the discretion of the principal investigator.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of myelofibrosis with myeloid metaplasia (MMM), defined by all of the following:

  * Leukoerythroblastic blood picture
  * Fibrosis involving \> 1/3 sectional area of bone marrow biopsy
  * Splenomegaly (unless patient has undergone prior splenectomy)
  * Philadelphia chromosome negative
  * No myelodysplastic syndrome
  * No systemic disorders associated with marrow fibrosis
* Red blood cell transfusion dependent, defined by 1 of the following:

  * Patient has required ≥ 2 units of red blood cells every 4 weeks within the past 8 weeks
  * Hemoglobin ≤ 8 g/dL on ≥ 3 occasions (≥ 2 weeks apart ) over the past 8 weeks
* No evidence of disease transformation to acute myelogenous leukemia, defined as \> 20% blasts in bone marrow and/or peripheral blood

PATIENT CHARACTERISTICS:

Performance status

* ECOG 0-3

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count \> 1,000/mm\^3
* Platelet count \> 50,000/mm\^3

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST or ALT ≤ 2 times ULN (unless due to extramedullary hematopoiesis in the liver)

Renal

* Creatinine ≤ 1.5 times ULN

Cardiovascular

* No New York Heart Association grade III-IV heart disease

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment
* No serious, uncontrolled medical condition
* No patients who are considered potentially unreliable or with a history of noncompliance to medical regimens

PRIOR CONCURRENT THERAPY:

Biologic therapy

* More than 2 weeks since prior interferon alfa

Chemotherapy

* No concurrent chemotherapy except hydroxyurea to control elevated blood counts

Endocrine therapy

* More than 4 weeks since prior corticosteroids, danazol, or other androgens for MMM

Other

* More than 4 weeks since other prior treatment for MMM
* No other concurrent experimental drug therapy for MMM

Primary outcomes:
measure: Percentage of Participants With Major and/or Minor Erythroid Responses at 3, 6, and 12 Months of Therapy
timeFrame: At 3,6, and 12 months of therapy
Secondary outcomes:
measure: Reduction in Marrow Fibrosis and Decrease in Spleen Size
timeFrame: After 6 and 12 months of therapy
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Michael Mauro, MD
role: PRINCIPAL_INVESTIGATOR
References: