Background: \- MLN4924 is an experimental cancer drug. It may help kill lymphoma cells and make them more sensitive to chemotherapy. EPOCH R is a combination chemotherapy drug. It has been effective in treating some cases of large B-cell lymphoma. This research will look at two things. The first is the effect of MLN4924 on its own in treating large B-cell lymphoma. The second is the safe dose and effect of MLN4924 and EPOCH-R in combination when treating large B-cell lymphoma. Objectives: * To study how MLN4924 affects large B-cell lymphoma tumors. * To compare the effects of MLN 4924 alone and MLN4924 plus standard EPOCH-R chemotherapy. Eligibility: \- Individuals at least 18 years of age who have large B-cell lymphoma that will be treated with chemotherapy. Design: * Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, tumor samples, and imaging studies. * Participants will receive MLN4924 for a maximum of six 21-day cycles of treatment. Each cycle involves a dose of MLN4924 twice a week for 2 weeks, followed by a 1-week rest period. Participants will be monitored with frequent blood tests and imaging studies. * Participants who do not benefit from MLN4924 alone will have MLN4924 along with EPOCH-R chemotherapy for up to six cycles of treatment.
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Assess response of MLN4924 in relapsed/refractory DLBCL
Timeframe: 4 years
Assess toxicity and safe tolerated dose of MLN4924 and DA-EPOCH-R
Timeframe: 4 years
Assess ORR (CR/PR) and PFS of MLN4924 and DA-EPOCH-R in relapsed/refractory DLBCL
Timeframe: 4 years