Inclusion Criteria:

- Diagnosis of relapsed or refractory diffuse large B-cell lymphoma (transformed large
cell lymphoma allowed)

- Must have received ≥ 1 and ≤ 6 prior therapeutic regimens

- No patients who are eligible for potentially curative treatment with bone marrow
transplantation, unless patient refuses transplant option

- No active CNS involvement by lymphoma

- ECOG performance status of 0-2

- Life expectancy > 3 months

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.0 g/dL

- Serum bilirubin < 1.5 times upper limit of normal (ULN)

- AST or ALT < 2.5 times ULN

- Fertile patients must agree to use adequate contraception (hormonal, barrier method
of birth control, or abstinence) prior to study entry, for the duration of study
participation, and for 4 weeks (female) and 16 weeks (male) after completion of
selumetinib

- Negative pregnancy test

- Not pregnant or nursing

- HIV-positive patients allowed provided CD4 count > 400 and have no AIDS-defining
illnesses (other than non-Hodgkin lymphoma)

- No other active infection

- No cardiac conditions, including any of the following:

- Uncontrolled hypertension (blood pressure ≥ 150/95 mm Hg despite optimal
therapy)

- NYHA class II-IV heart failure

- Prior or concurrent cardiomyopathy

- Baseline LVEF ≤ 50%

- Atrial fibrillation with heart rate > 100 bpm

- Unstable ischemic heart disease (myocardial infarction within 6 months prior to
starting treatment, or angina requiring > once weekly nitrates)

- QTc interval > 450 msecs or other factors that increase the risk of QT
prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family
history of long QT interval syndrome)

- No history of a serious medical or psychiatric illness likely to interfere with
participation in this clinical study

- No recent history of refractory nausea and vomiting, chronic gastrointestinal
diseases (e.g., inflammatory bowel disease), or significant bowel resection that
would preclude adequate absorption

- No concurrent vitamin E supplements or multivitamin supplements that provide a total
daily dose in excess of 100% of the recommended daily allowance for vitamin E

- More than 21 days since prior chemotherapy, radiotherapy, immunotherapy, or systemic
biologic anticancer therapy

- Prior autologous stem cell transplantation allowed, but no prior allogeneic stem cell
transplant

- No prior MEK, Ras, or Raf inhibitors

- At least 1 month wash-out interval since another investigational product, systemic
treatment, or radiotherapy

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent drugs that alter CYP450 3A4 (or cannot be changed to drugs that do not
alter CYP450 3A4)

- No concurrent drugs that may significantly prolong the QTc