Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients

An Open-Label, Randomized, Phase 2 Study to Assess the Effectiveness of RCHOP With or Without VELCADE in Previously Untreated Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma Patients

This is a randomized, open-label, multi-center, phase 2 study of RCHOP with or without VELCADE in adult patients with previously untreated non-(Germinal B-Cell-like) GCB Diffuse Large B-cell Lymphoma (DLBCL). The study will determine whether the addition of VELCADE to RCHOP improves progression-free survival (PFS) in patients with non-GCB DLBCL.

The drug tested in this study is called bortezomib (VELCADE®). VELCADE® was tested in people who have Non-Germinal Center B-Cell-like Diffuse Large B-Cell Lymphoma. This study looked at the efficacy of RCHOP [rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone] with or without VELCADE®.

The study enrolled 206 patients. Participants were enrolled in one of the two open label treatment groups:

• RCHOP
• Vc-RCHOP [bortezomib (VELCADE®), rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone]

Participants received treatment for up to six, 21-day cycles.

This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 48 months. Participants made multiple visits to the clinic, and were followed for progression free survival and overall survival until patient withdrawal, death, or 2 years after the last participant was enrolled.

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

Inclusion Criteria:

• Patients with previously untreated DLBCL that has been sub classified as the non-GCB subtype.
• At least 1 measurable tumor mass.
• Availability of paraffin block with sufficient tumor tissue.
• No evidence of central nervous system lymphoma.
• Eastern Cooperative Oncology Group (ECOG) performance status of < or equal to 2.
• Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
• Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

Exclusion Criteria:

• Diagnosed or treated for a malignancy other than DLBCL within 2 years of first dose or evidence of active malignancy other than DLBCL.
• Peripheral neuropathy of Grade 2 or greater.
• Known history of human immunodeficiency virus (HIV) infection, unless receiving highly active antiretroviral therapy (HAART).
• Active infection requiring systemic therapy.
• Major surgery within 2 weeks before first dose.
• Patients with a left ventricular ejection fraction (LVEF) or less than 45%.
• Myocardial infarction with 6 months of enrollment or evidence of current uncontrolled cardiovascular conditions as described in the protocol.
• History of allergic reaction/ hypersensitivity attributable to boron, mannitol, polysorbate 80 or sodium citrate dehydrate, or anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab.