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

A Multicenter Open-Label Phase 1b/2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Lenalidomide and Rituximab in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

This Phase 1b/2 study is designed to assess the safety and efficacy of ibrutinib in combination with lenalidomide and rituximab in subjects with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not eligible for transplant.

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 computed tomography (CT) scan (>1.5 cm in longest dimension)
• prothrombin time/international normalized ratio (PT/INR) < 1.5 x upper limit of normal (ULN) and partial thromboplastin time (PTT; activated partial thromboplastin time [aPTT]) <1.5 x ULN
• Men and women ≥18 years of age
• Eastern Cooperative Oncology Group (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.