diffuse large B-cell lymphoma (DLBCL) MedDRA version: 21.0 Level: PT Classification code 10012822 Term: Diffuse large B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
Conditions
Sponsors
Seagen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 the most recent 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. For subjects with transformed DLBCL (subtype k), at least the last systemic therapy used must have been for DLBCL. - Participants must be HSCT or CAR-T ineligible according to the investigator and must meet at least one of the following criteria: 1. 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 received HSCT or CAR-T therapy 2. Active disease following induction and salvage chemotherapy 3.Inadequate stem cell mobilization (for HSCT) 4. Relapse following prior HSCT or CAR-T 5. Unable to receive CAR-T therapy due to financial, geographic, insurance or manufacturing issues - Participants must have tumor tissue submitted to the central pathology lab for the determination of CD30 expression. - 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 >1.5 cm by computed tomography (CT), as assessed by the site radiologist within 28 days of Day 1. Other protocol defined inclusion criteria may apply. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 320 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
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. 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 - Participants 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 core antigen (HBsAg) negative but hepatitis B surface 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). Participants who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks. - Participants with previous allogeneic HSCT if they meet either of the following criteria: 1.<100 days from HSCT 2.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. 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 - Grade 2 or higher peripheral sensory or motor neuropathy at baseline Other protocol defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Evaluate and compare progression-free survival (PFS) between the 2 treatment arms in the intent-to-treat (ITT) population - 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 - Evaluate and compare the complete response (CR) rate between the 2 treatment arms - Evaluate and compare duration of response between the 2 treatment arms - Evaluate the safety and tolerability of the 2 treatment arms;Primary end point(s): - PFS per blinded independent central review (BICR) in the ITT population - PFS per BICR in the CD30-positive population.;Timepoint(s) of evaluation of this end point: - Up to 1 year - Up to 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - ORR per BICR - OS in the ITT population - OS in the CD30+ population - CR rate - Duration of objective response - Incidence, severity, and seriousness of adverse events (AEs);Timepoint(s) of evaluation of this end point: - Up to 1 year - Up to 18 months - Up to 18 months - Up to 1 year - Up to 1 year - Up to 1 year | — |
Countries
Australia, Belgium, Canada, Czech Republic, Denmark, France, Germany, Italy, Korea, Republic of, Netherlands, Poland, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactSeagen Clinical Trial Information
Seagen Inc.
Outcome results
None listed