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

A Multicenter Study of Ibrutinib and Lenalidomide in Combination With DA-EPOCH-R in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

This is a Phase 1b/2, open-label, non-randomized multicenter study to assess the safety and efficacy of ibrutinib and lenalidomide in combination with DA-EPOCH-R in subjects with relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL).

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