Clinical Trial: Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open-label, Phase 1b/2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, and Ofatumumab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small

Brief Summary: The purpose of this study is to determine the efficacy and safety of a fixed-dose, daily regimen of orally administered PCI-32765 combined with ofatumumab in subjects with relapsed/refractory CLL/SLL and related diseases

Detailed Summary:
Sponsor: Pharmacyclics LLC.

Current Primary Outcome:

• Percentage of Participants Achieving Response [ Time Frame: The median follow-up time on study for all treated participants is 12.5 (range 0.5-19.6) months ]
  The primary endpoint for the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR), CR with incomplete blood count recovery (Cri), or partial response (PR), according to the guidelines from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL1) published in 2008 for CLL participants and International Working Group for non-Hodgkin's lymphoma (IWG NHL) 2007 criteria for SLL participants, with the modification that treatment-related lymphocytosis will not be considered progressive disease, as evaluated by the investigators. Assessment of disease is based on radiological exams, physical exam, hematological evaluations and, when appropriate, bone marrow results.
• Safety During Dose-Limiting Toxicity (DLT) Observation Period [ Time Frame: 56 days for Group 1 and 28 days for Group 2 ]
  Number of dose-limiting toxicities observed in the first 6 participants enrolled in treatment Groups 1 and 2

Original Primary Outcome: Response and safety of PCI-32765 [ Time Frame: 1-3 cycles after last dose of study drug ]

Current Secondary Outcome:

• Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: From first dose of study treatment to within 30 days of last dose or until study closure ]
  Number of participants who had experienced at least one treatment emergent AE
• Progression Free Survival (PFS) at 12 Months [ Time Frame: From first dose of study treatment until disease progression, death, or until 12 months ]

  Progressive disease for CLL (Hallek) is characterized by ≥1 of the following:

  • Appearance of any new lesion, eg lymph nodes (> 1.5 cm), de novo hepatomegaly or splenomegaly, or other organ infiltrates

  • Increase of ≥50%

    • in longest diameter of any previous site
    • in hepatomegaly or splenomegaly
    • in blood lymphocytes with ≥5x109/L B cells with enlarging lymph node, liver, or spleen

  Progressive disease for B cell lymphoma (Cheson) is characterized by any new lesion or increase by ≥ 50% of previously involved sites from nadir:

  • Appearance of a new lesion(s) >1.5 cm in any axis, ≥ 50% increase in the SPD of >1 node, or ≥50% increase in longest diameter of a previously identified node >1 cm in short axis
  • Lesions PET+ if FDG-avid lymphoma or PET+ before therapy
  • 50% increase from nadir in the SPD of any liver or spleen lesions
  • New or recurrent BM involvement
  • Increase of ≥50% in blood lymphocytes with ≥5x109/L B cells within enlarging lymph node, liver, or spleen

Original Secondary Outcome:

• Pharmacokinetic/Pharmacodynamic assessments [ Time Frame: during 1-2 cycles ]
  Designed as safety issue Pharmacodynamics of PCI-32765 (ie, drug occupancy of Btk and effect on biologicial market 1/2) of PCI-32765.
• Tumor Response [ Time Frame: at the end of Cycles 2,4 and 6 (28 days for each cycle) ]
  Overall response rate as defined by recent guidelines on CLL

Dates:
Date Received: October 7, 2010
Date Started: December 2010
Date Completion:
Last Updated: May 28, 2015
Last Verified: May 2015