A Phase 2 Clinical Trial of Rituximab, Cyclophosphamide, Bortezomib (VELCADE®), and Dexamethasone (R-CyBor-D) in Relapsed Low Grade and Mantle Cell Lymphoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed relapsed or refractory follicular lymphoma (grade I or II),
mantle cell lymphoma (MCL), or lymphoplasmacytic lymphoma (Waldenstrom
macroglobulinemia [WM])

- MCL confirmed by cyclin D1 staining or fluorescent in situ hybridization
[t(11;14)]

- Measurable disease, defined as lymph nodes ≥ 2.0 cm in at least one dimension by CT
scan, PET/CT scan, or MRI

- Patients with WM without lymphadenopathy must have > 10% lymphocytes,
lymphoplasmacytic cells, or plasma cells on a bone marrow aspirate/biopsy AND
quantitative IgM ≥ 400 mg/dL

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy > 3 months

- ANC ≥ 1,200/mm^3

- Platelet count ≥ 75,000/mm^3

- Hemoglobin ≥ 8.0 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin ≤ 2.0
mg/dL

- Alkaline phosphatase ≤ 3 times ULN

- AST ≤ 3 times ULN

- Creatinine ≤ 1.5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No comorbid systemic illness or other severe concurrent disease that, in the judgment
of the investigator, would exclude the patient from participating in this study or
would interfere significantly with the proper assessment of safety and adverse events
of the prescribed study regimen

- No known HIV positivity

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable or uncontrolled angina pectoris

- Cardiac arrhythmias, including severe uncontrolled ventricular arrhythmias

- Psychiatric illness/social situation that would preclude compliance with study
requirements

- No hypersensitivity to bortezomib, boron, or mannitol

- No myocardial infarction within the past 6 months

- No NYHA class III-IV heart failure

- No evidence of acute ischemia by ECG

- No active conduction system abnormalities

- No other malignancy within the past 3 years, except for the following:

- Completely resected basal cell or squamous cell carcinoma of the skin

- In situ malignancy

- Curatively treated prostate cancer deemed to be at low risk

PRIOR CONCURRENT THERAPY:

- More than 14 days since prior investigational drugs

- At least 4 weeks since prior anticancer therapy, including radiotherapy, hormonal
therapy, or surgery

- No other concurrent investigational agents as treatment for the primary malignancy

- No concurrent therapy for other malignancies, except hormonal therapy