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Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL (ECHELON-3)

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ClinicalTrials.gov Identifier: NCT04404283
Recruitment Status : Recruiting
First Posted : May 27, 2020
Last Update Posted : July 20, 2021
Sponsor:
Information provided by (Responsible Party):
Seagen Inc.

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.

Patients 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," patients and their doctors will not know whether a patient gets brentuximab vedotin or placebo. All patients in the study will get rituximab and lenalidomide. These are drugs that can be used to treat DLBCL.


Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Drug: Brentuximab vedotin Drug: Rituximab Drug: Lenalidomide Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : August 20, 2020
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : April 30, 2027


Arm Intervention/treatment
Experimental: Experimental Arm
Brentuximab vedotin + lenalidomide + rituximab
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

Active Comparator: Control Arm
Placebo + lenalidomide + rituximab
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




Primary Outcome Measures :
  1. PFS per blinded independent central review (BICR) in the ITT population [ Time Frame: Approximately 1 year ]
    Time from the date of randomization to the date of first documentation of PD per BICR or to death due to any cause, whichever occurs first.

  2. PFS per BICR in the CD30-positive population [ Time Frame: Approximately 1 year ]
    Time from the date of randomization to the date of first documentation of PD per BICR or to death due to any cause, whichever occurs first.


Secondary Outcome Measures :
  1. Objective response rate (ORR) per BICR [ Time Frame: Approximately 1 year ]
    Proportion of subjects with complete response (CR) or partial response (PR) according to the Lugano Criteria for Response Assessment (Cheson 2014).

  2. Overall survival (OS) in the ITT population [ Time Frame: Approximately 18 months ]
    Time from the date of randomization to date of death due to any cause.

  3. OS in the CD30+ population [ Time Frame: Approximately 18 months ]
    Time from the date of randomization to date of death due to any cause.

  4. Complete response (CR) rate [ Time Frame: Approximately 1 year ]
    Proportion of participants with CR according to the Lugano Criteria for Response Assessment (Cheson 2014)

  5. Duration of objective response [ Time Frame: Approximately 1 year ]
    Time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (Cheson 2014) or death due to any cause, whichever comes first.

  6. Incidence of adverse events [ Time Frame: Approximately 1 year ]
    Any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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 will need to have a formalin-fixed paraffin-embedded tumor tissue (obtained ≤4 weeks before Day 1) submitted to the central pathology lab.
  • 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. 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04404283


Contacts
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Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
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Sponsors and Collaborators
Seagen Inc.
Investigators
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Study Director: Robert Sims, MD Seagen Inc.
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Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT04404283    
Other Study ID Numbers: SGN35-031
First Posted: May 27, 2020    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seagen Inc.:
Seattle Genetics
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Lenalidomide
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors