A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Ibrutinib; Placebo; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone (or equivalent)
Intervention description: 560 mg capsules administered by mouth once daily (21-day cycles); 4 matched capsules administered by mouth once daily (21-day cycles); 375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles); 750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles); 50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles); 1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles); 100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 838.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoma; B-cell lymphoma; Non-germinal center B-cell subtype; Diffuse large B-cell lymphoma; Bruton's tyrosine kinase inhibitor; PCI-32765; JNJ-54179060; Ibrutinib; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Summary:

      The purpose of this study is to evaluate if ibrutinib administered in combination with
      rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the
      clinical outcome in newly diagnosed patients with non-germinal center B-cell subtype (GCB) of
      diffuse large B-cell lymphoma (DLBCL) selected by immunohistochemistry (IHC) or newly
      diagnosed patients with activated B cell-like (ABC) subtype of DLBCL identified by gene
      expression profiling (GEP) or both populations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  No prior treatment for diffuse B-cell lymphoma (DLBCL)

          -  Histologically-confirmed non-germinal center B-cell subtype DLBCL

          -  Stage II (not candidates for local x-ray therapy), III, or IV disease by the Ann Arbor
             Classification

          -  At least 1 measurable site of disease according to Revised Response Criteria for
             Malignant Lymphoma

          -  Revised International Prognostic Index score of >=1

          -  Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2

          -  Hematology and biochemical laboratory values within protocol-defined parameters prior
             to random assignment and at baseline

          -  Left ventricular ejection fraction within institutional normal limits, as determined
             by echocardiography or multiple uptake gated acquisition (MUGA) scan

          -  Agrees to protocol-defined use of effective contraception (for women, these
             restrictions apply for 12 months after the last dose of rituximab or 1 month after the
             last dose of study drug, whichever is later; for men, these restrictions apply for 12
             months after the last dose of rituximab or 3 months after the last dose of study drug,
             whichever is later)

          -  Men must agree to not donate sperm during and after the study for 12 months after the
             last dose of rituximab or 3 months after the last dose of study drug, whichever is
             later

          -  Women of childbearing potential must have a negative serum or urine pregnancy test at
             screening

        Exclusion Criteria:

          -  Major surgery within 4 weeks of random assignment

          -  Known central nervous system or primary mediastinal lymphoma

          -  Prior history of indolent lymphoma

          -  Diagnosed or treated for malignancy other than DLBCL, except: malignancy treated with
             curative intent and with no known active disease present for >=3 years before random
             assignment; adequately treated non-melanoma skin cancer or lentigo maligna without
             evidence of disease; adequately treated carcinoma in situ without evidence of disease

          -  History of stroke or intracranial hemorrhage within 6 months prior to random
             assignment

          -  Requires anticoagulation with warfarin or equivalent vitamin K antagonists

          -  Requires treatment with strong CYP3A inhibitors

          -  Prior anthracycline use >=150 mg/m2

          -  Clinically significant cardiovascular disease such as uncontrolled or symptomatic
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
             screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by
             the New York Heart Association Functional Classification

          -  Known history of human immunodeficiency virus or active hepatitis C virus or active
             hepatitis B virus infection or any uncontrolled active systemic infection requiring
             intravenous antibiotics

          -  Women who are pregnant or breastfeeding

          -  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