Bortezomib, Rituximab, Cyclophosphamide, and Prednisone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
Leukemia, Lymphoma
About this trial
This is an interventional treatment trial for Leukemia focused on measuring recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent small lymphocytic lymphoma, recurrent marginal zone lymphoma, Waldenstrom macroglobulinemia, recurrent mantle cell lymphoma, refractory chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of 1 of the following: Chronic lymphocytic leukemia (CLL) B-cell small lymphocytic leukemia (SLL) Any marginal zone lymphoma Grade 1-3A follicular lymphoma Waldenstrom's macroglobulinemia Mantle cell lymphoma No transformed indolent lymphoma Assessable disease (phase I) Measurable disease (phase I and II), defined as ≥ one lesion that can be accurately measured in ≥ 1 dimension as ≥ 2 cm by conventional techniques OR ≥ 1 cm by spiral CT scan Lymph nodes measuring ≤ 1 cm in the short axis are considered normal Relapsed or refractory disease Must have received at least 1 prior therapeutic regimen but no more than 3 prior conventional cytotoxic therapy regimens No known brain metastases or meningeal disease PATIENT CHARACTERISTICS: Karnofsky performance status > 50% Absolute neutrophil count > 1,000/mcl (more than 500/mcl if known lymphomatous involvement) Platelet count ≥ 50,000/mcl Total bilirubin < 1.5 times upper limit of normal (ULN) (less than 5 mg/dL if known history of Gilbert's disease) AST and ALT ≤ 2.5 times ULN (4 times ULN if liver involvement) Creatinine < 1.5 times ULN OR creatinine clearance > 50 mL/min Patients may have febrile episodes up to 38.5ºC without evidence of active infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No New York Heart Association class III or IV congestive heart failure No uncontrolled intercurrent illness, including any of the following: Ongoing or active infection Cerebrovascular accident or transient ischemic attack within 6 months of study entry Unstable angina pectoris Cardiac arrhythmia EKG evidence of acute ischemia Psychiatric illness/social situations that would limit compliance with study requirements No uncontrolled hypertension requiring active manipulation of antihypertensive medications No known or active HIV infection No history of hypersensitivity to bortezomib, boron, or mannitol No peripheral neuropathy > grade 2 No other malignancy within the past 5 years except curatively treated non life-threatening malignancies, such as cutaneous basal cell or squamous cell carcinoma or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from prior therapy Prior stem cell transplantation allowed Preparative cytoreductive and high-dose therapies considered 1 prior therapy At least 4 weeks since prior cytotoxic chemotherapy (6 weeks since prior nitrosoureas or mitomycin C) At least 12 weeks since prior radioimmunotherapy One prior course comprising tositumomab or ibritumomab tiuxetan allowed At least 1 week since prior palliative steroids for NHL No therapeutic monoclonal antibodies (e.g., rituximab, tositumomab, ibritumomab, alemtuzumab, etc.) within 3 months of study entry Patients treated with monoclonal antibodies within 3 months allowed provided disease progressed on this therapy AND no treatment received 7 days prior to study entry Seven days since prior rituximab (for patients enrolled in phase I portion) No major surgery within 4 weeks of study entry No other concurrent investigational agents No other concurrent anticancer therapy
Sites / Locations
- Winship Cancer Institute of Emory University
- Memorial Sloan-Kettering at Basking Ridge
- Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
- Memorial Sloan-Kettering Cancer Center @ Suffolk
- Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
- Memorial Sloan-Kettering Cancer Center
- Memorial Sloan-Kettering at Mercy Medical Center
- Memoral Sloan Kettering Cancer Center@Phelps
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm I
Arm II
Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.