Diffuse large B-cell lymphoma (DLBCL) MedDRA version: 20.0 Level: LLT Classification code 10012855 Term: Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) System Organ Class: 100000004864
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18-80 years and willingness to comply with the study protocol procedures, including patient reported outcome measures - Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses by 2016 WHO classification of lymphoid neoplasms: o DLBCL, not otherwise specified (NOS) including germinal center B-cell type, activated B-cell type o T-cell/histiocyte-rich large B-cell lymphoma o Epstein-Barr virus-positive DLBCL, NOS o ALK-positive large B-cell lymphoma o HHV8-positive DLBCL, NOS o High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma) o High-grade B-cell lymphoma, NOS - Availability of archival or freshly collected tumor tissue before study enrollment - International Prognostic Index score of 2-5 - Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2 - Life expectancy >= 12 months - At least one bi-dimensionally measurable lesion, defined as >= 1.5 cm in its longest dimension as measured by computed tomography or magnetic resonance imaging - Left ventricular ejection fraction >= 50% on cardiac multiple-gated acquisition scan or cardiac echocardiogram - Adequate hematologic function - For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 525
Exclusion criteria
Exclusion criteria: - Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products - Prior organ transplantation - Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease - History of indolent lymphoma - Current diagnosis of the following: 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, CNS lymphoma (primary or secondary involvement), primary effusion DLBCL, and primary cutaneous DLBCL - Prior treatment with cytotoxic drugs within 5 years of screening for any condition or prior use of any anti-CD20 antibody - Prior use of any monoclonal antibody within 3 months of the start of Cycle 1; any investigational therapy within 28 days prior to the start of Cycle 1; vaccination with live vaccines within 28 days prior the start of Cycle 1 - Prior therapy for DLBCL - Corticosteroid use >30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control - 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 - Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis - History or presence of an abnormal electrocardiogram that is clinically significant in the investigator’s opinion - Known active bacterial, viral, fungal, mycobacterial, parasitic or other infection 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 - Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator’s judgment - Any of the abnormal laboratory values such as international normalization ratio > 1.5 x upper limit of normal (ULN) in the absence of therapeutic anticoagulation, Partial thromboplastin time or activated partial thromboplastin time > 1.5 x ULN in the absence of a lupus anticoagulant, Serum aspartate aminotransferase and alanine aminotransferase >= 2.5 x ULN, Total bilirubin >= 1.5 x ULN, Serum creatinine clearance < 40 mL/min - Patients with suspected active or latent tuberculosis - Positive test results for chronic hepatitis B infection, hepatitis C, human T-lymphotrophic 1 virus - Known history of HIV seropositive status - Patients with a history of progressive multifocal leukoencephalopathy - Pregnancy or lactation or intending to become pregnant during study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of polatuzumab vedotin plus rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to progression-free survival (PFS);Secondary Objective: • To evaluate the efficacy of polatuzumab vedotin plus R-CHP compared with R-CHOP with respect to secondary efficacy endpoints • To evaluate the safety of polatuzumab vedotin plus R-CHP compared with R-CHOP • To characterize the pharmacokinetics of polatuzumab vedotin • To evaluate the immune response to polatuzumab vedotin ;Primary end point(s): 1. Progression-free survival as assessed by the investigator by using the Lugano Response Criteria for Malignant Lymphoma;Timepoint(s) of evaluation of this end point: 1. Up to approximately 65 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. 2-year progression-free survival rate as determined by the investigator 2. Event-free survival (efficacy) as determined by the investigator 3. Complete response rate at end of treatment by fluorodeoxyglucose positron emission tomography as determined by blinded independent central review and by the investigator 4. Overall Survival 5. Disease-free survival 6. Duration of Response 7. Event-free survival (all causes) 8. Time to deterioration in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 questionnaire (EORTC QLQ-C30) physical functioning and fatigue and Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LymS) 9. Proportion of patients achieving meaningful improvement in EORTC QLQ-C30 physical functioning and fatigue, and FACT-Lym LymS 10. EORTC QLQ-C30 rate of treatment-related symptoms and FACT/ Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity peripheral neuropathy rate 11. Incidence, nature, and severity of adverse events, with severity determined through use of National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0) 12. Incidence of peripheral neuropathy rates and severity determined through use of NCI CTCAE v4.0 13. Incidence and nature of study drug discontinuation, dose reduction, and dose delay due to adverse events 14. Dose intensities of study drugs 15. Plasma and/or serum concentration of polatuzumab vedotin related analytes at specified time points 16. Incidence of Anti-drug antibodies (ADAs) to polatuzumab vedotin during the study relative to the prevalence of ADAs to polatuzumab vedotin at baseline ;Timepoint(s) of evaluation of this end point: 1. At 24 months 2-7. Up to approximately 65 months 8-10. Day 1 of Cycle 1, 2, 3 and 5, at treatment completion, and post-treatment visits 11-14. Up to approximately 65 months 15-16. Day 1 of Cycle 1 and 4, at treatment completion and at 3 mon | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Hong Kong, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Portugal, Russian Federation, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed