Study of Bortezomib in Combination With Cyclophosphamide and Rituximab

The Study Drugs: Bortezomib is designed to block a protein that plays a role in cell function and growth. This may cause cancer cells to die. Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die. Rituximab is designed to attach to lymphoma cells, which may cause them to die. Study Drug Administration: If you are found to be eligible to take part in this study, you will receive all of the study drugs preferably through a central venous catheter (CVC) that will be left in place the entire time that you are receiving the study drugs. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. You will sign a separate consent form for this procedure, which will describe the procedure and the risk in more detail. You will receive rituximab by vein over 6 hours on Day 1 of every 21-day study cycle. You will receive bortezomib by vein over 3 to 5 seconds, after you have received rituximab on Day 1 of every cycle. You will also receive bortezomib on Days 4, 8, and 11 of every cycle. You will receive cyclophosphamide by vein over 3 hours 2 times each day (6 hours total each day) on Days 2, 3, and 4 of every cycle. On these days, you will also receive mesna by vein non-stop. Mesna is a drug that protects the bladder from damage by chemotherapy drugs. It is used to decrease the risk of bleeding in the bladder. You will receive G-CSF (filgrastim - a drug that is used to help build your white blood cell counts and prevent infections) as an injection under the skin starting 24-36 hours after you receive bortezomib. You will receive filgrastim 1 time each day until your white blood cell counts recover. Study Visits: At each study visit, you will be asked about how you are feeling and about any other drugs that you may be taking. Throughout the study, blood (about 1 tablespoon each time) will be drawn 2-3 times a week for routine tests. Within 2 days before each cycle, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your weight and vital signs. * You will complete the questionnaire about nervous system side effects. * Your performance status will be recorded. * Blood (about 2 tablespoons) will be drawn for routine tests. After every 2 cycles, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your weight and vital signs. * Your performance status will be recorded. * You will have a chest x-ray or CT scans to check the status of the disease. These scans may be of your head, neck, chest, stomach, and/or pelvis. The CT scan at Cycle 4 will only occur if the doctor thinks it is needed. * Blood (about 5 teaspoons) will be drawn for routine tests. * If your doctor thinks it is needed, you will have a bone marrow biopsy/aspirate to check the status of the disease. * If your doctor thinks it is needed, you will have an ECHO or a multigated radionuclide angiography (MUGA) scan and/or an ECG. You will have an exam of the colon (colonoscopy) to check the status of the disease after Cycle 2. Biopsy samples (about 3-6) of the colon will be taken during this exam to check the status of the disease. After Cycles 2, 6, and/or 8, if your doctor thinks it is needed, you will have a positron emission tomography (PET) scan to check the status of the disease. After Cycle 6, you will be taken off study if the disease is in "complete remission" (if the disease has disappeared). Otherwise, you may receive 2 more cycles of study treatment. If you are receiving 2 more cycles, if colonoscopy was done after Cycle 2 and it showed lymphoma, you will have another colonoscopy after Cycle 6 and Cycle 8 to check the status of the disease. Biopsy samples (about 3-6) of the colon will be taken during this exam to check the status of the disease. Length of Study: You will receive the study drugs for up to 8 cycles (about 8 months). You will be taken off study early if the disease gets worse or intolerable side effects occur before Cycle 8, or if the disease is in complete remission after Cycle 6. End-of-Treatment Visit: After you have finished receiving the study drugs, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your weight and vital signs. * You will complete the questionnaire about nervous system side effects. * Your performance status will be recorded. * You will have a chest x-ray or CT scans to check the status of the disease. * Blood (about 5 teaspoons) will be drawn for routine tests. * If your doctor thinks it is needed, you will have a bone marrow biopsy/aspirate to check the status of the disease. * If your doctor thinks it is needed, you will have an ECHO or a MUGA scan and/or an ECG. Follow-Up Visits: After you have finished receiving the study drugs, you will have follow-up visits according to the following schedule: * Every 3 months during Year 1 after treatment. * Every 4 months during Year 2 after treatment * Every 6 months during Years 3-4 after treatment. * Every 12 months after Year 4 after treatment. At each of the follow-up visits, the following tests and procedures will be performed: * You will have a complete physical exam, including measurement of your weight and vital signs. * You will complete the questionnaire about nervous system side effects. * Your medical history will be recorded * Your performance status will be recorded. * Blood (around 1 tablespoon) will be drawn for routine tests. * You will have a chest x-ray to check the status of the disease. * You will have CT scans of the head, neck, chest, abdomen, and pelvis to check the status of the disease. * If the doctor thinks it is needed, you will have a bone marrow aspirate/biopsy to check the status of the disease. This is an investigational study. All of the drugs used in this study are FDA approved and commercially available for the treatment of various types of lymphoma. The use of this drug combination is investigational. Up to 46 patients will take part in this multicenter study. All will be enrolled at M. D. Anderson.