The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

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Hematological Malignancies

Brentuximab vedotin

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
NCT04404283

Active Not-enrolling

Globe
Locations

United States, Australia, Belgium, Canada, Czechia, Denmark, France, Germany, Italy, Korea, Republic of, Netherlands, Poland, Spain, Switzerland, Taiwan, United Kingdom

Study design

Participant Group/Arm

EXPERIMENTAL: Experimental Arm

Brentuximab vedotin + lenalidomide + rituximab

Intervention/Treatment

DRUG: Brentuximab vedotin

1.2 mg/kg administered into the vein (IV; intravenously) infusion every 3 weeks

DRUG: Rituximab

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.

DRUG: Lenalidomide

20 mg given by mouth (orally) daily

Participant Group/Arm

ACTIVE_COMPARATOR: Control Arm

Placebo + lenalidomide + rituximab

Intervention/Treatment

DRUG: Rituximab

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.

DRUG: Lenalidomide

20 mg given by mouth (orally) daily

OTHER: Placebo

Administered via intravenous infusion every 3 weeks

Key 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 DLB
  • 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

Key dates

Study start date
  • August 2020
Estimated primary completion date
  • April 2027

Key endpoints

Primary Outcome Measures
Outcome Measure

Overall survival (OS)

Measure Description

OS is defined as the time from the date of randomization to date of death due to any cause

Time Frame

Approximately 2 years

Secondary Outcome Measures:
Outcome Measure

Progression-free survival (PFS)

Measure 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)

Time Frame

Approximately 1 year

Outcome Measure

Objective response rate (ORR)

Measure 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).

Time Frame

Approximately 1 year

Outcome Measure

Complete response (CR) rate

Measure Description

Proportion of participants with best response of CR according to investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014)

Time Frame

Approximately 1 year

Outcome Measure

Duration of response (DOR)

Measure 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.

Time Frame

Approximately 1 year

Outcome Measure

Incidence of adverse events

Measure 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.

Time Frame

Approximately 1 year

Outcome Measure

OS in CD30+ participants

Measure Description

Time from the date of randomization to date of death due to any cause.

Time Frame

Approximately 2 years

Number of participants

240

Collaborators and investigators

Sponsor: Seagen Inc.

Collaborator: None

This information is current as of June 4th 2024.