• Progression-free survival and overall survival 5 years after completion of study treatment [ Designated as safety issue: No ]
  

• Response at the end of dose-adjusted induction therapy [ Designated as safety issue: No ]
  
• Response and toxicity at the end of maintenance therapy [ Designated as safety issue: Yes ]
  
• Response and progression-free survival of bortezomib at disease progression in the observation treatment arm 5 years after completion of study treatment [ Designated as safety issue: No ]
  
• Time to non-protocol treatment in the maintenance and observation treatment arms 5 years after completion of study treatment [ Designated as safety issue: No ]
  
• Correlation of mircoarray and proteomic findings with clinical outcomes as measured by cDNA microarray 5 years after completion of study treatment [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Compare the progression-free and overall survival of patients with previously untreated mantle cell lymphoma treated with single-agent bortezomib followed by dose-adjusted induction therapy comprising bortezomib in combination with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) and maintenance therapy comprising bortezomib vs observation.

Secondary

• Determine the response in patients treated with single-agent bortezomib administered before dose-adjusted induction therapy.
• Determine toxicity of dose-adjusted induction therapy in these patients.
• Determine the response in patients treated with dose-adjusted induction therapy.
• Determine the response and progression-free survival of patients initially randomized to the observation arm who are subsequently treated with bortezomib at the onset of disease progression.
• Compare the time to non-protocol treatment in patients treated with maintenance therapy comprising bortezomib vs observation.
• Correlate microarray and proteomic findings with clinical outcome of patients treated with these regimens.

OUTLINE: This is a randomized study.

• Single-agent bortezomib: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8 and 11.
• Dose-adjusted induction therapy: Beginning within 22-28 days after the start of single-agent bortezomib, patients receive rituximab IV on day 1 followed by etoposide, doxorubicin, and vincristine IV continuously over 96 hours on days 1-4. Patients also receive bortezomib IV over 3-5 seconds on days 1 and 4; oral prednisone twice daily on days 1-5; and cyclophosphamide IV over 15 minutes on day 5. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until day 15 or until blood counts recover. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• Maintenance therapy: Patients who achieve at least a partial response to dose-adjusted induction therapy are randomized to 1 of 2 arms.

  • Arm I: Beginning 8-12 weeks after the completion of dose-adjusted induction therapy, patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 8 weeks for up to 18 months in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo observation only. Patients with disease progression receive bortezomib as in arm I. Treatment repeats every 4 weeks for up to 18 months.

After completion of study treatment, patients are followed every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 80 patients (40 per maintenance treatment arm) will be accrued for this study within 2 years.