Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL

Phase 3

Active, not recruiting

• Conditions: Diffuse Large B-cell Lymphoma
• Interventions: Drug: Rituximab; Drug: Brentuximab vedotin; Drug: Lenalidomide; Other: Placebo

• Registration Number: NCT04404283
• Lead Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-21
• Study First Submitted QC: 2020-05-21
• Study First Posted: 2020-05-27
• Study Start: 2020-08-20
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-06
• Last Update Posted: 2025-06-10
• Primary Completion: 2025-11-30
• Study Completion: 2025-11-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 241

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.

  • For participants with transformed DLBCL, 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 participant 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. 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.

  • 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, 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Arm	Lenalidomide	Brentuximab vedotin + lenalidomide + rituximab
Control Arm	Lenalidomide	Placebo + lenalidomide + rituximab
Control Arm	Placebo	Placebo + lenalidomide + rituximab
Control Arm	Rituximab	Placebo + lenalidomide + rituximab
Experimental Arm	Brentuximab vedotin	Brentuximab vedotin + lenalidomide + rituximab
Experimental Arm	Rituximab	Brentuximab vedotin + lenalidomide + rituximab

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	Approximately 2 years	OS is defined as the time from the date of randomization to date of death due to any cause

Secondary Outcome Measures

Name	Time	Method
OS in CD30+ participants	Approximately 2 years	Time from the date of randomization to date of death due to any cause.
Progression-free survival (PFS)	Approximately 1 year	PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. Assessment of PD will be performed by the investigator based on the Lugano Criteria for Response Assessment (Cheson 2014)
Incidence of adverse events	Approximately 1 year	Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Objective response rate (ORR)	Approximately 1 year	Proportion of participants with best response of complete response (CR) or partial response (PR) according to investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014).
Complete response (CR) rate	Approximately 1 year	Proportion of participants with best response of CR according to investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014)
Duration of response (DOR)	Approximately 1 year	Time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression by investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014) or death due to any cause, whichever occurs first.

Trial Locations

Locations (171)

Central Alabama Research; 🇺🇸 Birmingham, Alabama, United States

Alabama Oncology; 🇺🇸 Birmingham, Alabama, United States

Arizona Oncology Associates, PC - NAHOA; 🇺🇸 Goodyear, Arizona, United States

The Oncology Institute of Hope & Innovation - California; 🇺🇸 Riverside, California, United States

University of California Davis; 🇺🇸 Sacramento, California, United States

Lundquist Institute/Harbor-UCLA; 🇺🇸 Torrance, California, United States

Florida Cancer Specialists - South Region; 🇺🇸 Fort Myers, Florida, United States

Florida Cancer Specialists - North Region; 🇺🇸 Saint Petersburg, Florida, United States

Florida Cancer Specialists - East West Palm Beach, FL (SCRI); 🇺🇸 West Palm Beach, Florida, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Scroll for more (161 remaining)