Bortezomib in Treating Patients With Advanced Myeloproliferative Disorders

• Status: Completed
• Trial end date: 2008-11-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Bortezomib may stop the growth of abnormal cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the abnormal cells.

PURPOSE: This clinical trial is studying the side effects and how well bortezomib works in treating patients with advanced myeloproliferative disorders.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bortezomib

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced myeloproliferative disorder, including 1 of the following subtypes:

• Myelofibrosis with myeloid metaplasia defined by the following criteria:

• Evaluable or symptomatic disease as evidenced by ≥ 1 of the following:

• Anemia, defined as hemoglobin < 10 g/dL OR erythrocyte-transfusion dependence, defined as requiring 1 transfusion within the past 8 weeks

• Symptomatic palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) requiring treatment* NOTE: *Subjective but painful enough to mandate intervention

• Chronic myelomonocytic leukemia (CMML) defined by the following criteria:

• Absence of an imatinib mesylate-sensitive molecular abnormality for CMML (i.e., t[5;12], t[5;10], t[1;5], and t[5;7]) confirmed by fluorescent in situ hybridization (FISH) or standard cytogenetic bone marrow analysis within the past 18 months

• Symptomatic disease as evidenced by ≥ 1 of the following:

• Anemia, defined as hemoglobin < 10 g/dL OR erythrocyte-transfusion dependence, defined as requiring 1 transfusion within the past 8 weeks

• Palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) requiring treatment* NOTE: *Subjective but painful enough to mandate intervention

• Leukocytosis associated with ascites, serositis, pleural effusions, vasculitis, or other overt manifestation

• Systemic mast cell disease defined by the following criteria:

• Absence of the FIP1LI-PDGFRA mutation as confirmed by FISH

• Evaluable and symptomatic disease requiring therapy, as evidenced by involvement with organs other than skin (i.e., heart, bowel, peripheral blood, liver/spleen, or marrow)

• Debilitating mast cell mediator symptoms not responsive to standard therapy such as antihistamines

• Absence of t(9;22) translocation as confirmed by FISH or standard cytogenetic peripheral blood or marrow analysis at any prior time point

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Not incarcerated in a municipal, county, state, or federal prison

• Absolute neutrophil count ≥ 1,000/mm³

• Platelet count ≥ 75,000/mm³

• Creatinine ≤ 2.0 mg/dL

• Total or direct bilirubin ≤ 2.0 mg/dL

• AST and ALT ≤ 3 times upper limit of normal (unless clinically attributed to hepatic extramedullary hematopoiesis)

• No baseline peripheral or autonomic neuropathy ≥ grade 2

• No other condition or laboratory abnormality that would place the patient at unacceptable risk or confound the ability to interpret study data

• No hypersensitivity to boron, mannitol, or bortezomib

• No myocardial infarction within the past 6 months

• No New York Hospital Association class III-IV heart failure

• No uncontrolled angina

• No severe uncontrolled ventricular arrhythmia

• No evidence of acute ischemia or active conduction system abnormality by ECG

• ECG screening abnormalities must be documented as not medically relevant

• No other serious medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

• At least 14 days since prior chemotherapy (e.g., interferon alfa, anagrelide, or other myelosuppressive agent) or any other experimental therapy

• At least 14 days since prior growth factors

• At least 14 days since prior systemic use of corticosteroids

• More than 14 days since prior investigational drugs

• Concurrent hydroxyurea allowed for ≤ 14 days during study therapy if clinically indicated for extreme leukocytosis control