Bortezomib and Fludarabine With or Without Rituximab in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hematopoietic/Lymphoid Cancer, Nodal Marginal Zone B-cell Lymphoma
About this trial
This is an interventional treatment trial for Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Eligibility Criteria
Inclusion Criteria: Diagnosis of chronic lymphocytic leukemia (CLL) OR indolent non-Hodgkin's lymphoma (NHL) of any of the following subtypes: Follicular lymphoma: Grade I follicular small cleaved cell; Grade II follicular mixed cell; Grade II follicular large cell; Diffuse small cleaved cell; Small lymphocytic lymphoma; Lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia) AND Extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue [MALT] lymphoma); Nodal marginal zone B-cell lymphoma (monocytoid B-cell lymphoma); Splenic marginal zone lymphoma (splenic lymphoma with villous lymphocytes); Mantle cell lymphoma: No blastic phase mantle cell lymphoma Relapsed or refractory, progressive disease: First, second, or third relapse Measurable disease, meeting 1 of the following criteria: At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan (for NHL patients); OR: Lymphocytosis > 50,000/mm3 OR evidence of progressive bone marrow infiltration failure (e.g., hemoglobin 10 g/dL) OR thrombocytopenia (i.e., platelet count < 100,000/mm3) with > 30% infiltration of bone marrow by leukemia (for CLL patients) No measurable lymphadenopathy (for CLL and Waldenstrom's macroglobulinemia patients) No evidence of CNS lymphoma Performance status: ECOG 0-2 Life expectancy: More than 12 weeks No history of uncontrolled orthostatic hypotension No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No uncontrolled concurrent illness No grade 2 or greater neuropathy No history of allergy or anaphylaxis to mannitol, bortezomib, fludarabine, or boron No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance At least 4 weeks since prior monoclonal antibody (MoAB) therapy: Patients who have received MoAB therapy within the past 3 months must have documented disease progression since receiving this therapy No prior allogeneic stem cell transplantation More than 4 weeks since prior chemotherapy Prior fludarabine allowed At least 1 week since prior steroids At least 3 months since prior radio-immunotherapy More than 4 weeks since prior radiotherapy No prior bortezomib Absolute neutrophil count at least 1,500/mm3 Platelet count at least 75,000/mm3 (greater than 50,000/mm3 if lymphomatous bone marrow involvement is present) Bilirubin no greater than 2.0 mg/dL AST/ALT no greater than 4 times normal Creatinine clearance greater than 40 mL/min No other concurrent investigational agents or treatments for the malignancy No brain metastases OR: Quantitation of IgM paraprotein (for Waldenstrom's macroglobulinemia patients)
Sites / Locations
- Mercy Medical Center
- Case Western Reserve University
- Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
- Southwest General Health Center Ireland Cancer Center
- UHHS-Chagrin Highlands Medical Center
- University Suburban Medical Center
- UHHS-Westlake Medical Center
Arms of the Study
Arm 1
Experimental
Treatment (bortezomib, fludarabine, rituximab)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and fludarabine IV over 30 minutes on days 1-3 or 1-5. Patients may also receive rituximab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.