NCT04404283 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-07-22

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility 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 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Brentuximab vedotin + lenalidomide + rituximab
intervention Names
Drug: Brentuximab vedotin
Drug: Rituximab
Drug: Lenalidomide
label
Experimental Arm
type
EXPERIMENTAL
description
Placebo + lenalidomide + rituximab
intervention Names
Drug: Rituximab
Drug: Lenalidomide
Other: Placebo
label
Control Arm
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Experimental Arm
description
1.2 mg/kg administered into the vein (IV; intravenously) infusion every 3 weeks
name
Brentuximab vedotin
type
DRUG
arm Group Labels
Control Arm
Experimental Arm
description
375 mg/m\^2 administered via intravenous infusion on Cycle 1 Day 1. 1400 mg injected under the skin (subcutaneous) permitted every 3 weeks from Cycle 2 Day 1 through end of treatment.
name
Rituximab
type
DRUG
arm Group Labels
Control Arm
Experimental Arm
description
20 mg given by mouth (orally) daily
name
Lenalidomide
type
DRUG
arm Group Labels
Control Arm
description
Administered via intravenous infusion every 3 weeks
name
Placebo
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: TRIPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 239
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
OS is defined as the time from the date of randomization to date of death due to any cause
measure
Overall survival (OS)
time Frame
Approximately 2 years

secondary Outcomes

description
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)
measure
Progression-free survival (PFS)
time Frame
Approximately 1 year
description
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).
measure
Objective response rate (ORR)
time Frame
Approximately 1 year
description
Proportion of participants with best response of CR according to investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014)
measure
Complete response (CR) rate
time Frame
Approximately 1 year
description
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.
measure
Duration of response (DOR)
time Frame
Approximately 1 year
description
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.
measure
Incidence of adverse events
time Frame
Approximately 1 year
description
Time from the date of randomization to date of death due to any cause.
measure
OS in CD30+ participants
time Frame
Approximately 2 years

Full study description

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.

Source references

references

citation
Bartlett NL, Hahn U, Kim WS, Fleury I, Laribi K, Bergua JM, Bouabdallah K, Forward N, Bijou F, MacDonald D, Portell CA, Ghesquieres H, Nowakowski G, Yasenchak CA, Patterson M, Ho L, Rustia E, Fanale M, Jie F, Kim JA. Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2025 Mar 20;43(9):1061-1072. doi: 10.1200/JCO-24-02242. Epub 2025 Jan 7.
pmid
39772655
type
DERIVED
citation
Ward JP, Berrien-Elliott MM, Gomez F, Luo J, Becker-Hapak M, Cashen AF, Wagner-Johnston ND, Maddocks K, Mosior M, Foster M, Krysiak K, Schmidt A, Skidmore ZL, Desai S, Watkins MP, Fischer A, Griffith M, Griffith OL, Fehniger TA, Bartlett NL. Phase 1/dose expansion trial of brentuximab vedotin and lenalidomide in relapsed or refractory diffuse large B-cell lymphoma. Blood. 2022 Mar 31;139(13):1999-2010. doi: 10.1182/blood.2021011894.
pmid
34780623
type
DERIVED