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Purpose

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).

Condition

Eligibility

Eligible Ages
Between 18 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
R-CHP plus Vincristine Placebo plus Polatuzumab Vedotin 		Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) intravenously (IV), placebo for vincristine IV, rituximab 375 milligrams per square meter (mg/m^2) IV, cyclophosphamide 750 mg/m^2 IV, and doxorubicin 50 mg/m^2 IV on Day 1 and prednisone 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of every 21-day cycle for 6 cycles. Rituximab 375 mg/m^2 IV will be administered as monotherapy in Cycles 7 and 8.
  • Drug: Polatuzumab Vedotin
    Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm.
    Other names:
    • DCDS4501A; anti-CD79b-VC-MMAE
  • Drug: Rituximab
    Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
  • Drug: Cyclophosphamide
    Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
  • Drug: Doxorubicin
    Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
  • Drug: Vincristine Placebo
    Placebo matching to vincristine will be administered as per the schedule specified in the respective arm.
  • Drug: Prednisone
    Prednisone PO will be administered as per the schedule specified in the respective arm.
Placebo Comparator
R-CHOP plus Polatuzumab Vedotin Placebo 		Participants will receive placebo for polatuzumab vedotin, rituximab 375 mg/m^2 IV, cyclophosphamide 750 mg/m^2 IV, doxorubicin 50 mg/m^2 IV, and vincristine 1.4 mg/m^2 IV (maximum 2 milligrams per dose [mg/dose]) on Day 1 and prednisone 100 mg/day PO on Days 1-5 of every 21-day cycle for 6 cycles. Rituximab 375 mg/m^2 IV will be administered as monotherapy in Cycles 7 and 8.
  • Drug: Rituximab
    Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
  • Drug: Cyclophosphamide
    Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
  • Drug: Doxorubicin
    Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
  • Drug: Vincristine
    Vincristine IV infusion will be administered as per the schedule specified in the respective arm.
  • Drug: Prednisone
    Prednisone PO will be administered as per the schedule specified in the respective arm.
  • Drug: Polatuzumab vedotin Placebo
    Placebo matching to polatuzumab vedotin will be administered as per the schedule specified in the respective arm.

More Details

Status
Active, not recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.