Bortezomib, Combination Chemotherapy, and Rituximab as First-Line Therapy in Treating Patients With Stage III or Stage IV Follicular Non-Hodgkin's Lymphoma

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular non-Hodgkin's lymphoma meeting the following criteria:

  • Stage III or IV disease
  • Grade 1, 2, or 3 disease requiring systemic first-line treatment
  • No transformation to diffuse large cell lymphoma

• At least 1 bidimensionally measurable lesion meeting 1 of the following criteria:

  • Lymph nodes > 1.5 cm x 1.0 cm by physical exam or CT scan
  • Other non-nodal lesion ≥ 1.0 cm x 1.0 cm by MRI or CT scan OR ≥ 1.0 cm x 1.0 cm (e.g., skin lesions or nodules) by physical exam

• Must have a medical indication for treatment, as indicated by 1 of the following:

  • Presence of constitutional symptoms that are attributed to lymphoma (e.g., B symptoms, including night sweats, fever, weight loss, fatigue, or pain)
  • Lymphadenopathy that requires treatment based on presence of associated symptoms, potential threat to organ function (e.g., ureteric compromise from retroperitoneal disease), or degree of enlargement (i.e., > 5 cm)
  • Impairment of normal organ function (e.g., impaired hematopoiesis due to marrow involvement by lymphoma or from splenomegaly and hypersplenism)
  • Immune-related complications of lymphoma that require therapy
  • Rate of disease progression for which observation is deemed inappropriate
• No history of any other lymphoproliferative disorder or evidence of transformation to an aggressive histology lymphoma
• No known CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Platelet count ≥ 75,000/mm^3*
• Absolute neutrophil count ≥ 1,000/mm^3*
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST or ALT ≤ 2.5 times ULN (5 times ULN if liver involvement with lymphoma)

• Able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French

  • Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study

• No history of other malignancies, except for the following:

  • Adequately treated nonmelanoma skin cancer
  • Curatively treated in situ cancer of the cervix
  • Ductal carcinoma in situ of the breast (as long as radiation limitation is not exceeded)
  • Other solid tumors curatively treated with no evidence of disease for > 5 years
• No history of allergic reactions attributed to compounds containing boron or mannitol
• No history of an unusual or severe allergic reaction to rituximab or similar agent
• No pre-existing neuropathy ≥ grade 2
• No known HIV infection

• No other serious illness or medical condition that would preclude study participation, including any of the following:

  • Active, uncontrolled bacterial, fungal, or viral infection
  • Significant cardiac dysfunction
  • Cardiovascular disease NOTE: *Exceptions will be allowed for values below these thresholds in patients with marrow involvement by lymphoma or lymphoma-related hypersplenism

PRIOR CONCURRENT THERAPY:

• No prior systemic therapy for lymphoma
• No prior bortezomib, cyclophosphamide, or vincristine

• At least 4 weeks since prior radiotherapy that involved ≤ 25% of functioning bone marrow and recovered

  • Exceptions may be made for low-dose, nonmyelosuppressive radiotherapy or if the irradiated field is not a significant marrow-bearing area
• At least 2 weeks since prior major surgery
• No other concurrent anticancer therapy, investigational agents, corticosteroids (except for physiologic replacement or antiemesis), cytotoxic chemotherapy, or immunotherapy