A Study of PCI-32765 (Ibrutinib) in Combination With Either Bendamustine and Rituximab or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Participants With Previously Treated Indolent Non-Hodgkin Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Bendamustine; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; PCI-32765 (Ibrutinib); Placebo
Intervention description: 90 milligram per meter square (mg/m^2) administered intravenously on Days 1 to 2 of Cycles 1 to 6.; 375 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.; 750 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.; 50 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.; 1.4 mg/m^2 (maximum total 2 mg) administered intravenously on Day 1 of Cycles 1 to 6.; 100 mg administered orally on Days 1 to 5 of Cycles 1 to 6.; 560 mg (4*140 mg) capsules administered orally once daily, continuously starting on Cycle 1, Day 1.; Placebo (4 capsules) matched to ibrutinib administered orally once daily, continuously starting on Cycle 1, Day 1.
Intervention MeSH terms: Prednisone; Cyclophosphamide; Bendamustine Hydrochloride; Rituximab; Doxorubicin; Vincristine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 405.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoma; Follicular lymphoma; Marginal zone lymphoma; Indolent Non-Hodgkin lymphoma; PCI-32765; Ibrutinib; Bendamustine; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; R-CHOP

Summary:

      The purpose of this study is to evaluate the efficacy and safety of PCI-32765 (ibrutinib)
      administered in combination with either bendamustine and rituximab (BR) or rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in adult participants
      with previously treated indolent Non-Hodgkin lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of B-cell indolent Non-Hodgkin lymphoma with
             histological subtype limited to follicular lymphoma or marginal zone lymphoma, at
             initial diagnosis and without evidence of pathological transformation or clinical
             signs suggesting transformation

          -  At least 1 prior treatment with a CD20 antibody combination chemo-immunotherapy
             regimen

          -  Disease that has relapsed or was refractory after prior chemo-immunotherapy

          -  At least 1 measurable site of disease according to Revised Response Criteria for
             Malignant Lymphoma 2007

          -  Eastern Cooperative Oncology Group performance status grade 0 or 1

          -  Laboratory values within protocol-defined parameters

          -  Agrees to protocol-defined use of effective contraception

          -  Men must agree not to donate sperm during and after the study for 6 months after the
             last dose of bendamustine, 12 months after the last dose of rituximab, or 3 months
             after the last dose of study medication, whichever is later

          -  Women of childbearing potential must have a negative serum or urine pregnancy test at
             Screening

        Exclusion Criteria:

          -  Prior treatment according to protocol-defined criteria

          -  Unable to receive background chemotherapy based on prior treatment history and cardiac
             function

          -  Known central nervous system lymphoma

          -  Diagnosed or treated for malignancy other than indolent Non-Hodgkin lymphoma

          -  History of stroke or intracranial hemorrhage within 6 months prior to randomization

          -  Requires anticoagulation with warfarin or equivalent Vitamin K antagonists

          -  Requires treatment with strong CYP3A inhibitors

          -  Clinically significant cardiovascular disease

          -  Known history of human immunodeficiency virus or active hepatitis C virus (HCV;
             ribonucleic acid [RNA] polymerase chain reaction [PCR]-positive) or active hepatitis B
             virus (HBV; DNA PCR-positive) infection or any uncontrolled active systemic infection
             requiring intravenous antibiotics

          -  Any life-threatening illness, medical condition, or organ system dysfunction which, in
             the Investigator's opinion, could compromise the participant's safety, interfere with
             the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue
             risk

          -  Women who are pregnant or breastfeeding