Brentuximab Vedotin plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBC

Phase 1

Conditions: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
MedDRA version: 20.0Level: HLTClassification code: 10012819Term: Diffuse large B-cell lymphomas Class: 10029104
MedDRA version: 21.0Level: PTClassification code: 10012822Term: Diffuse large B-cell lymphoma refractory Class: 100000004864
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Therapeutic area: Phenomena and Processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

Registration Number: CTIS2023-503384-41-00

Lead Sponsor: Seagen Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 218

Inclusion Criteria

Subjects 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 the most recent local pathology assessment for the purposes of study eligibility and stratification. The following subtypes of DLBCL are eligible for enrollment: a. Not otherwise specified (NOS) b. Intravascular large B-cell lymphoma c. DLBCL associated with chronic inflammation d. EBV-positive NOS e. ALK-positive f. T-cell-/histiocyte-rich large B-cell lymphoma g. Primary mediastinal large B-cell lymphoma h. High-grade B-cell lymphoma with translocations of MYC and BCL2 and/or BCL6 (double-/triple-hit lymphoma) i. High-grade NOS B-cell lymphomas j. Primary cutaneous DLBCL (leg type) k. DLBCL arising from transformed indolent lymphomas/leukemias, Subjects who can father children, under the following conditions: a. Must agree not to donate sperm starting at time of informed consent and continuing throughout the study period and for at least 12 months after the final dose of study drug. b. If sexually active with a person of childbearing potential in a way that could lead to pregnancy, must consistently use 2 methods of birth control (see Appendix C) starting at time of informed consent and continuing throughout the study and for at least 12 months after the final dose of study drug. c. If sexually active with a person who is pregnant or breastfeeding, must consistently use one of the contraception options (see Appendix C) starting at time of informed consent and continuing throughout the study and for at least 12 months after the final dose of study drug, The following requirements for subjects who are known to be human immunodeficiency virus (HIV) positive: ? CD4+ T-cell counts =350 cells/mm3 within 28 days of Day 1 ? No acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months ? On established highly active antiretroviral therapy for at least 4 weeks with an HIV viral load less than 400 copies/mL within 28 days of Day 1 (see Section 5.6.2 for subjects receiving strong CYP3A inhibitors)., The subject must provide written informed consent, Subjects must have R/R disease following =2 lines of prior systemic therapy. For subjects with transformed DLBCL (subtype k), at least the last systemic therapy used must have been for DLBCL., Subjects must be HSCT or CAR-T ineligible according to the investigator and must meet at least one of the following criteria: a. One or more co-morbidities, including cardiac, pulmonary, renal or hepatic dysfunction that in the opinion of the Investigator make the subject medically unfit to receive HSCT or CAR-T therapy. b. Active disease following induction and salvage chemotherapy c. Inadequate stem cell mobilization (for HSCT) d. Relapse following prior HSCT or CAR-T e. Unable to receive CAR-T therapy due to financial, geographic, insurance, or manufacturing issues., Subjects must have tumor tissue submitted to the central pathology lab for the determination of CD30 expression, which will be centrally determined by visual assessment for any detectable level of CD30 on tumor cells by IHC. The most recent biopsy available that contains viable DLBCL tissue should be submitted. If the CD30 results from the central pathology lab are not available prior to randomization, the subject may be stratified based on % CD30 expression from the local pathology lab. Subjects who are stratified based on l

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. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 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, 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, Previous treatment with brentuximab vedotin or lenalidomide. a. Previous treatment with other vedotin-based ADCs is permitted if the last dose is at least 6 months prior to Day 1, 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, pulmonary embolism, 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 (see Appendix D)., Grade 2 or higher peripheral sensory or motor neuropathy at baseline, 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, History of progressive multifocal leukoencephalopathy (PML)., 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, 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, Subjects who are breastfeeding, Known hypersensitivity to any study drug or excipient contained in the drug formulation of the study drugs, Any contraindication to associated study treatments, Known to be positive for hepatitis B by surface antigen expression. Subjects who are hepatitis B surface antigen (HBsAg) negative but hepatitis B core antibody (HBcAb) positive are eligible, but should start hepatitis B prophylaxis therapy prior to receiving the first dose of rituximab. Known to be positive for hepatitis C (HCV) infection (either confirmed 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate and compare progression-free survival (PFS) between the 2 treatment arms in the intent-totreat (ITT) population.<br>Evaluate and compare PFS between the 2 treatment arms in the CD30-positive population.;Secondary Objective: Evaluate and compare the objective response rate (ORR) between the 2 treatment arms in the ITT population., Evaluate and compare overall survival (OS) between the 2 treatment arms in the ITT population., Evaluate and compare OS between the 2 treatment arms in the CD30-positive population.;Primary end point(s): PFS per blinded independent central review (BICR) in the ITT population, PFS per BICR in the CD30-positive population

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):ORR per BICR;Secondary end point(s):OS in the ITT population;Secondary end point(s):OS in the CD30+ population

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