Ibrutinib in Combination With Lenalidomide and Rituximab in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Phase 1b: In the dose escalation portion of the study, various cohorts with escalating doses
of lenalidomide may be explored, using the 3+3+3 principle for dose determination.

Phase 2: This will be conducted as an international, multicenter, open-label study. Eligible
subjects will receive ibrutinib, lenalidomide and rituximab.

Inclusion Criteria:

- Pathologically confirmed relapsed/ refractory DLBCL

- Must have previously received first line treatment regimen

- Must be ineligible for high dose therapy/ stem cell transplantation

- Measurable disease sites on CT scan (>1.5 cm in longest dimension)

- PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN

- Men and women ≥18 years of age

- ECOG < 2

- Adequate hepatic and renal function

- Adequate hematologic function

Exclusion Criteria:

- Medically apparent central nervous system lymphoma or leptomeningeal disease

- History of allogeneic stem-cell (or other organ) transplantation

- Any chemotherapy, external beam radiation therapy, or anticancer antibodies within 2
weeks

- Radio- or toxin-immunoconjugates within 10 weeks

- Concurrent enrollment in another therapeutic investigational study or have previously
taken ibrutinib and/or lenalidomide.