Investigator left institution. 7 patients accrued and there is insufficient data to analyze.

This study seeks to determine the maximum tolerated dose of bortezomib in combination with rituximab, ifosfamide, carboplatin, and etoposide for patients with relapsed or primary refractory aggressive B-Cell Non-Hodgkin's lymphoma (diffuse large B-cell, mantle cell, follicular grade III, transformed lymphoma). Subjects will be enrolled in cohorts of 3 at each bortezomib dose level, starting at 1 mg/m(2), and escalating to 1.3, 1.5, and 1.7 mg/m(2). Bortezomib will be given on days 1 (prior to rituximab) and 4, rituximab 375 mg/m(2)/day on days 2, 3, and 4 of a 21-day cycle. They will also receive filgrastim on days 6-13 or pegfilgrastim on day 6.

Inclusion Criteria:

• Aggressive B-Cell Lymphoma, CD-20 positive, in first relapse or refractory to first-line chemotherapy

  • Diffuse large B-cell Lymphoma, Mantle cell lymphoma, Follicular lymphoma (Grade III), Transformed Follicular Lymphoma
  • Rituximab is allowed
  • Prior radiation is allowed

• 18-70 years of age

• ECOG performance status of 0-2

• HIV seronegative

• Measurable disease on CT scan by international working group response criteria

• No CNS involvement

• Subject is considered to be a candidate for autologous stem cell transplant in the opinion of the treating physician

• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control

• Male subject agrees to use an acceptable method of contraception for the duration of the study

Exclusion Criteria:

• Platelet count of <75 x 10(9)/L
• Absolute neutrophil count of <1.0 x 10(9)/L
• Calculated or measured creatinine clearance of <60 mL/minute within 14 days before enrollment
• Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Subject has hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding.
• Subject has been treated with more than one prior chemotherapy regimen.
• Subject has received other investigational drugs with 14 days before enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.