Clinical Trial 18539

Cancer Type: Malignant Hematology
Interventions:748645 (Ibrutinib); ACP-196 (Acalabrutinib); Ibrutinib (Imbruvica); PCI-32765 (Ibrutinib)

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Javier Pinilla-Ibarz

Overview

Study Title

A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase 3 Study of ACP-196 Versus Ibrutinib in Previously Treated Subjects with High Risk Chronic Lymphocytic Leukemia

Summary

The purpose of this study is to determine if an experimental drug: ACP-196 is safe and effective in the treatment of Chronic Lymphocytic Leukemia (CLL).

Objective

To assess whether ACP-196 is non-inferior to ibrutinib with respect to progression-free survival (PFS) based on independent review committee (IRC) assessment in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) with high-risk prognostic markers. The IRC will use the International Workshop on Chronic Lymphocytic Leukemia Criteria (IWCLL, Hallek 2008) with incorporation of the clarification for treatment-related lymphocytosis (Cheson 2012)¿hereafter referred to as IWCLL 2008 criteria.

Inclusion Criteria

  • Men and women ≥ 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Diagnosis of Chronic Lymphocytic Leukemia (CLL) that meets published diagnostic criteria (Hallek 2008).
  • Must have ≥ 1 of the following high-risk prognostic factors: Presence of 17p del by central laboratory; Presence of 11q del by central laboratory
  • Active disease meeting ≥ 1 of the following International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment
  • Must have received ≥ 1 prior therapies for CLL
  • Measurable nodal disease by computed tomography (CT)
  • Adequate hematologic and organ function

  • Exclusion Criteria

  • Known central nervous system (CNS) lymphoma or leukemia
  • Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura
  • Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor or a BCL-2 inhibitor
  • Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug
  • Prior radio- or toxin-conjugated antibody therapy
  • Prior allogeneic stem cell or autologous transplant.
  • Major surgery within 4 weeks before first dose of study drug
  • Prior malignancy, except for adequately treated lentigo maligna melanoma, non-melanomatous skin cancer, in situ cervical carcinoma or other malignancy treated with no evidence of active disease > 3 years before Screening and at low risk for recurrence
  • Currently active clinically significant cardiovascular disease within 6 months before first dose with study drug
  • Known history of infection with HIV
  • History of stroke or intracranial hemorrhage within 6 months before randomization
  • History of bleeding diathesis
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 28 days of first dose of study drug
  • Requires treatment with a strong CYP3A4 inhibitor/inducer