A Randomized, Double-blind, Placebo-Controlled, Active-Comparator, Multicenter, Phase 3 Study of Brentuximab Vedotin or Placebo in Combination With Lenalidomide and Rituximab in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
A Randomized, Double-blind, Placebo-Controlled, Active-Comparator, Multicenter, Phase 3 Study of Brentuximab Vedotin or Placebo in Combination With Lenalidomide and Rituximab in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Participants in this study will have diffuse large B-cell lymphoma (DLBCL) that has come back or not gotten better with treatment. The trial will study whether brentuximab vedotin plus two drugs works better to treat this type of cancer than the two drugs alone.
Participants will be randomly assigned to get either brentuximab vedotin or placebo. The placebo will look like brentuximab vedotin, but has no medicine in it. Since the study is "blinded," participants and their doctors will not know whether a participant gets brentuximab vedotin or placebo. All participants in the study will get rituximab and lenalidomide. These are drugs that can be used to treat DLBCL.
Inclusion Criteria:
Participants with relapsed or refractory diffuse and transformed large B-cell lymphoma (R/R DLBCL). DLBCL and cell of origin (GCB versus non-GCB) will be histologically determined by local pathology assessment for the purposes of study eligibility and stratification.
Participants must have R/R disease following 2 or more lines of prior systemic therapy.
Participants must be HSCT or CAR-T ineligible according to the investigator and must meet at least one of the following criteria:
Participants must have tumor tissue submitted to the central pathology lab. The tumor tissue submitted should be from the most recent biopsy that contains DLBCL.
An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
Participants must have fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) and bidimensional measurable disease of at least 1.5 cm by computed tomography (CT), as assessed by the site radiologist within 28 days of Day 1.
Exclusion Criteria:
History of another malignancy within 2 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy
History of progressive multifocal leukoencephalopathy (PML)
Active cerebral/meningeal disease related to the underlying malignancy. Participants with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior CNS disease has been effectively treated and without progression for at least 3 months.
Any uncontrolled Grade 3 or higher (per NCI CTCAE version 5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study drug. Routine antimicrobial prophylaxis is permitted
Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed 3 weeks prior to first dose of study drug, unless underlying disease has progressed on treatment
Previous treatment with brentuximab vedotin or lenalidomide.
Current therapy with immunosuppressive medications (including steroids), other systemic anti-neoplastic, or investigational agents
a) Prednisone (or equivalent) ≤10 mg/day may be used for non-lymphomatous purposes
Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to the first dose of study drugs
Congestive heart failure, Class III or IV, by the NYHA criteria
Grade 2 or higher peripheral sensory or motor neuropathy at baseline
Sacramento, California 95817, United States
Baltimore, Maryland 21201, United States
Farmington Hills, Michigan 48334, United States
St Louis, Missouri 63110, United States
Montreal, Quebec H1T 2M4, Canada
Montreal, Quebec H4J 1C5, Canada
Nantes, Cedex 144093, France
Pessac, 33600, France
Vandœuvre-lès-Nancy, Cedex 54511, France
Villejuif, 94805 Cedex, France
Tricase, Lecce 73039, Italy
L'Hospitalet de Llobregat, Catalonia 08908, Spain
Birmingham, WEST Midlands B15 2TH, United Kingdom