a study comparing the efficacy and safety of polatuzumab vedotin with rituximab-cyclophosphamide, doxorubicin, and prednisone (r-chp) versus rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (r-chop) in participants with diffuse large b-cell lymphoma

Conditions: Diffuse Large B-Cell Lymphoma

Summary: this phase iii, randomized, double-blind, placebo-controlled study will compare the efficacy, safety, and pharmacokinetics of polatuzumab vedotin plus r-chp versus r-chop in participants with previously untreated diffuse large b-cell lymphoma (dlbcl).


Eligibility criteria:
inclusion criteria: * previously untreated participants with cluster of differentiation 20 (cd20)-positive dlbcl, including one of the following diagnoses by 2016 world health organization (who) classification of lymphoid neoplasms: dlbcl, not otherwise specified (nos) including germinal center b-cell type, activated b-cell type; t-cell/histiocyte-rich large b-cell lymphoma; epstein-barr virus-positive dlbcl, nos; anaplastic lymphoma kinase (alk)-positive large b-cell lymphoma; human herpesvirus-8 (hhv8)-positive dlbcl, nos; high-grade b-cell lymphoma with myc and b-cell lymphoma 2 (bcl2) and/or b-cell lymphoma 6 (bcl6) rearrangements (double-hit or triple-hit lymphoma); high-grade b-cell lymphoma, nos * availability of archival or freshly collected tumor tissue before study enrolment * international prognostic index (ipi) score of 2-5 * eastern cooperative oncology group (ecog) performance status of 0, 1, or 2 * life expectancy greater than or equal to (\>/=)12 months * left ventricular ejection fraction (lvef) \>/= 50 percent (%) on cardiac multiple-gated acquisition (muga) scan or cardiac echocardiogram (echo) * adequate hematologic function * female participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from donating eggs. * male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm. exclusion criteria: * history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products * contraindication to any of the individual components of chop, including prior receipt of anthracyclines * prior organ transplantation * current grade greater than (\>) 1 peripheral neuropathy by clinical examination * demyelinating form of charcot-marie-tooth disease * history of indolent lymphoma * history of follicular lymphoma grade 3b * b-cell lymphoma, unclassifiable, with features intermediate between dlbcl and classical hodgkin lymphoma (grey-zone lymphoma) * primary mediastinal (thymic) large b-cell lymphoma * burkitt lymphoma * prior treatment with cytotoxic drugs within 5 years of screening for any condition (example \[e.g.\], cancer, rheumatoid arthritis) or prior use of any anti-cd20 antibody * prior use of any monoclonal antibody within 3 months of the start of cycle 1 * prior therapy for dlbcl, with the exception of nodal biopsy * corticosteroid use \>30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control * participants with central nervous system (cns) lymphoma (primary or secondary involvement), primary effusion dlbcl, and primary cutaneous dlbcl * vaccination with live vaccines within 28 days prior to the start of cycle 1 * any investigational therapy within 28 days prior to the start of cycle 1 * history of other malignancy that could affect compliance with the protocol or interpretation of results * evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or pulmonary disease * recent major surgery (within 4 weeks prior to the start of cycle 1), other than for diagnosis * history or presence of an abnormal electrocardiogram (ecg) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction * known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or significant infections within 2 weeks before the start of cycle 1 * clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis * prior radiotherapy to the mediastinal/pericardial region * participants with suspected active or latent tuberculosis * positive test results for chronic hepatitis b and hepatitis c infection * known history of human immunodeficiency virus (hiv) seropositive status * positive results for the human t-lymphotrophic 1 virus (htlv-1) * participants with a history of progressive multifocal leukoencephalopathy