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) Estudio en fase III multicéntrico, aleatorizado, doble ciego, controlado con placebo y con comparador activo, de brentuximab vedotina o placebo en combinación con lenalidomida y rituximab en pacientes con linfoma difuso de células B grandes (LDCBG) recidivante o resistente
Key eligibility criteria include subjects aged 18 and older with relapsed/refractory (R/R) DLBCL with an eligible subtype; subjects must have ≥2 prior lines of therapy and must be ineligible for, or have declined, stem cell transplant and CAR-T therapy; subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2; subjects must have a 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.
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. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS ≥90%), such as carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. 2. History of progressive multifocal leukoencephalopathy (PML). 3. Active cerebral/meningeal disease related to the underlying malignancy. Subjects 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. Study SGN35-031 Clinical Protocol 11-Sep-2020 Brentuximab vedotin Seattle Genetics, Inc. - Confidential Page 23 of 75 4. 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. 5. 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. 6. Subjects who are breastfeeding. 7. Known hypersensitivity to any study drug or excipient contained in the drug formulation of the study drugs. 8. Known to be positive for hepatitis B by surface antigen expression. Known to be positive for hepatitis C infection (positive by polymerase chain reaction [PCR] or on antiviral therapy for hepatitis C within the last 6 months). Subjects who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks. 9. Subjects with previous allogeneic HSCT if they meet either of the following criteria:
? <100 days from HSCT
? Active acute or chronic graft-versus-host disease (GVHD) or receiving
immunosuppressive therapy as treatment for or prophylaxis against GVHD.
10. Previous treatment with brentuximab vedotin or lenalidomide. 11. 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.12. 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. 13. Congestive heart failure, Class III or IV, by the NYHA criteria (see Appendix D).14. Grade 2 or higher peripheral sensory or motor neuropathy at baseline.
15. Other serious underlying medical condition that, in the opinion of the investigator, would impair the subject’s ability to receive or tolerate the planned treatment, and complete study assessments.
