A Study of Participants With Lymphoma Who Take R-CHOP and Enzastaurin Compared to Participants Who Take R-CHOP Only

Inclusion Criteria:

Participants must:

1. Have a histologically confirmed diagnosis of DLBCL based on the World Health Organization classification (Harris et al. 1999) at the time of original diagnosis. Pathology must be reviewed and confirmed prior to enrollment at the investigational site where the participant is entered. Participants with a prior history of an indolent lymphoma or a histological diagnosis of follicular Grade 3 lymphoma will not be eligible for enrollment.
2. Have received no prior chemotherapy.
3. Have an International Prognostic Index (IPI) score ≥2 at time of original diagnosis.
4. Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology group (ECOG) scale.
5. Have adequate organ function as follows:

   * Hepatic: total bilirubin ≤1.5 times the upper limit of normal (x ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤1.5 x ULN, (≤5 x ULN, if liver involvement).
   * Renal: serum creatinine ≤1.5 x ULN.
   * Adequate bone marrow reserve: platelets ≥75 x 10\^9 per Liter (L), absolute neutrophil count (ANC) ≥1.0 x 10\^9 per L, unless there is bone marrow involvement.

   Exclusion Criteria:

   Participants must not:
6. Have received treatment within the last 30 days with a drug (not including enzastaurin) that has not received regulatory approval for any indication at the time of study entry.
7. Are receiving concurrent administration of any other systemic anticancer therapy.
8. Are pregnant or breastfeeding.
9. Are unable to swallow tablets.
10. Are unable to discontinue use of carbamazepine, phenobarbital, and phenytoin at least 14 days prior to study enrollment.