A Study of Ibrutinib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Ibrutinib; Bendamustine hydrochloride; Rituximab; Placebo
Intervention description: Type=exact number, unit=mg, number=420 , form=capsule, route=oral use. Capsule is taken once daily continuously.; Type=exact number, unit=mg, number=70 mg/m2, route=intravenous use. Administered intravenously on Cycle 1, Days 2-3 and Cycles 2-6, Days 1-2.; Type=exact number, unit=mg, number=375 mg/m2 and 500 mg/m2, route=intravenous use. Administered intravenously on Cycle 1, Day 1, and Cycles 2-6, Day 1, respectively.; Form=capsule, route=oral use. Capsule is taken once daily continuously.
Intervention MeSH terms: Rituximab; Bendamustine Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 578.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic lymphocytic leukemia; Small lymphocytic lymphoma; Relapsed or refractory chronic lymphocytic leukemia; Relapsed or refractory small lymphocytic lymphoma; Ibrutinib; PCI-32765; JNJ-54179060; Bruton's tyrosine kinase inhibitor; Bendamustine; Rituximab

Summary:

      The purpose of this study is to examine the safety and efficacy of Ibrutinib administered in
      combination with bendamustine and rituximab in patients with relapsed or refractory chronic
      lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)
             that meets protocol-defined criteria

          -  Active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic
             Leukemia 2008 criteria for requiring treatment

          -  Measurable nodal disease by computed tomography

          -  Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy
             consisting of at least 2 cycles of a chemotherapy-containing regimen

          -  Eastern Cooperative Oncology Group Performance Status score of 0 or 1

          -  Hematology and biochemical values within protocol-defined limits

          -  Agrees to protocol-defined use of effective contraception

          -  Women of childbearing potential must have negative blood or urine pregnancy test at
             screening

        Exclusion Criteria:

          -  Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks
             (immunotherapy)

          -  Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior
             randomization in any other clinical study evaluating ibrutinib

          -  The presence of deletion of the short arm of chromosome 17

          -  Patients previously treated with a bendamustine-containing regimen who did not achieve
             a response or who relapsed and required treatment within 24 months of treatment with
             that regimen

          -  Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant

          -  Received a hematopoietic stem cell transplant

          -  Known central nervous system leukemia/lymphoma or Richter's transformation

          -  Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia

          -  Chronic use of corticosteroids

          -  History of prior malignancy, except: malignancy treated with curative intent and with
             no known active disease present for >=3 years before randomization; adequately treated
             non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately
             treated cervical carcinoma in situ without evidence of disease

          -  History of stroke or intracranial hemorrhage within 6 months prior to randomization;
             or clinically significant cardiovascular disease

          -  Requires anticoagulation with warfarin or equivalent vitamin K antagonists or
             treatment with strong CYP3A4/5 inhibitors

          -  Known history of human immunodeficiency virus or hepatitis C, or active infection with
             hepatitis B or C

          -  Any uncontrolled active systemic infection or any life-threatening illness, medical
             condition, or organ system dysfunction which, in the investigator's opinion, could
             compromise the patient's safety, interfere with the absorption or metabolism of
             ibrutinib capsules, or put the study outcomes at undue risk

          -  A woman who is pregnant or breast feeding, or a man who plans to father a child while
             enrolled in this study or within 3 months after the last dose of study drug