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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 17, 2020

Detailed Description

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.

Interventions

  • Drug: Ibrutinib
  • Drug: Lenalidomide
  • Drug: Rituximab

Arms, Groups and Cohorts

  • Experimental: Phase 1: Dose Level -1
    • Ibrutinib PO+ Lenalidomide (PO) + Rituximab (IV)
  • Experimental: Phase 1: Dose Level 1
    • Ibrutinib PO+ Lenalidomide (PO) + Rituximab (IV)
  • Experimental: Phase 1: Dose Level 1+
    • Ibrutinib PO+ Lenalidomide (PO) + Rituximab (IV)
  • Experimental: Phase 1: Dose Level 2
    • Ibrutinib PO+ Lenalidomide (PO) + Rituximab (IV)
  • Experimental: 2Phase 1: Dose Level 3
    • Ibrutinib PO+ Lenalidomide (PO) + Rituximab (IV)
  • Experimental: Phase 2
    • Ibrutinib PO+ Lenalidomide (PO) + Rituximab (IV)

Clinical Trial Outcome Measures

Primary Measures

  • Phase 1: Determine the maximally tolerated dose (MTD) and /or the recommended Phase 2 (RP2) dose of lenalidomide in combination with fixed doses of ibrutinib and rituximab in subjects with relapsed or refractory DLBCL.
    • Time Frame: Up to 45 months
  • Phase 2: Overall response rate (ORR)
    • Time Frame: Up to 45 months

Secondary Measures

  • Phase 1: Overall response rate(ORR)
    • Time Frame: Up to 45 months
  • Phase 2: Duration of response (DOR)
    • Time Frame: Up to 45 months
  • Phase 2: Progression free survival (PFS)
    • Time Frame: Up to 45 months
  • Phase 2: Overall survival (OS)
    • Time Frame: Up to 45 months
  • Phase 2: Complete response (CR)
    • Time Frame: Up to 45 months
  • Phase 2: Safety and tolerability of ibrutinib in combination with lenalidomide and rituximab in subjects with relapsed or refractory non-GCB DLBCL.
    • Time Frame: Up to 45 months

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Pharmacyclics LLC.
  • Collaborator
    • Janssen Research & Development, LLC
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jutta K. Neuenburg, MD, PhD, Study Director, Pharmacyclics LLC.

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