Ibrutinib and Lenalidomide With Dose Adjusted EPOCH-R in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma

This is a Phase 1b, open-label, non-randomized multicenter study conducted in 2 parts. Part
1, will determine the MTD of the combination of ibrutinib, lenalidomide and DA-EPOCH-R in
subjects with DLBCL.

Ibrutinib will be administered at a fixed dose of 560 mg and lenalidomide will be
dose-escalated. DA-EPOCH-R will be given at standard doses.

For Part 2, the MTD determined in Part 1 will be the dose used for all subjects. If no MTD is
identified, then subjects in Part 2 will be treated with the maximum administered doses (MAD,
treatment doses from dose Level 4).

The primary objective for Part 2 is to determine the ORR of ibrutinib and lenalidomide in
combination with DA-EPOCH-R in subjects with ABC DLBCL as analyzed by gene expression
profiling when treated at recommended phase 2 dose (RP2D).

Major inclusion criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

- Pathologically confirmed relapsed/refractory DLBCL

- Subjects must have ≥1 measurable disease site on CT scan (≥ 1.5 cm in longest
dimension).

- Adequate hepatic and renal function:

- AST or ALT ≤2.5 x ULN

- Serum Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥60 mL/min/1.73

- Bilirubin ≤1.5 x ULN

- Adequate hematologic function:

- ANC >1,000 cells/mm3

- Platelets ≥75,000 cells/mm3

- Hemoglobin ≥8.0 g/dL

- Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be
≤1.5 x the upper limit of the normal range (ULN)

- Must be registered into the Revlimid REMS™program and be willing to comply with the
requirements of Revlimid REMS™.

Major Exclusion Criteria:

- Known central nervous system lymphoma

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

- Radio- or toxin-immunoconjugates within 10 weeks

- Prior allogenetic stem cell (or other organ) transplant within 6 months or any
evidence of active graft-versus-host disease or requirement for immunosuppressants
within 28 days prior to first dose of study drug