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
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
- Diffuse Large B-Cell Lymphoma
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
| Arm | Description | Assigned 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. |
|
|
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. |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Hoffmann-La Roche