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)

Phase 3

Withdrawn

• Conditions: DLBCL; Non Hodgkin Lymphoma; 10025320

• Registration Number: NL-OMON52039
• Lead Sponsor: Seagen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 4

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:
o 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
o Active disease following induction and salvage chemotherapy
o Inadequate stem cell mobilization (for HSCT)
o Relapse following prior HSCT or CAR-T
o 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.

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 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). 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 nonlymphomatous
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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Evaluate and compare PFS between the 2 treatment arms in the intent-to-treat<br /><br>(ITT) population<br /><br>Evaluate and compare PFS between the 2 treatment arms in the CD30-positive<br /><br>population</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Evaluate and compare OS between the 2 treatment arms in the ITT population<br /><br>* Evaluate and compare OS between the 2 treatment arms CD30-positive population<br /><br>* OS in the ITT population<br /><br>* OS in the CD30-positive population<br /><br>* Evaluate and compare objective response rate (ORR) between the 2 treatment<br /><br>arms in the ITT population</p><br>