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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04404283




Registration number
NCT04404283
Ethics application status
Date submitted
21/05/2020
Date registered
27/05/2020
Date last updated
18/06/2024

Titles & IDs
Public title
Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL
Scientific 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)
Secondary ID [1] 0 0
SGN35-031
Universal Trial Number (UTN)
Trial acronym
ECHELON-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Brentuximab vedotin
Treatment: Drugs - Rituximab
Treatment: Drugs - Lenalidomide
Other interventions - Placebo

Experimental: Experimental Arm - Brentuximab vedotin + lenalidomide + rituximab

Active comparator: Control Arm - Placebo + lenalidomide + rituximab


Treatment: Drugs: Brentuximab vedotin
1.2 mg/kg administered into the vein (IV; intravenously) infusion every 3 weeks

Treatment: Drugs: 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.

Treatment: Drugs: Lenalidomide
20 mg given by mouth (orally) daily

Other interventions: Placebo
Administered via intravenous infusion every 3 weeks
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
Approximately 2 years
Secondary outcome [1] 0 0
Progression-free survival (PFS)
Timepoint [1] 0 0
Approximately 1 year
Secondary outcome [2] 0 0
Objective response rate (ORR)
Timepoint [2] 0 0
Approximately 1 year
Secondary outcome [3] 0 0
Complete response (CR) rate
Timepoint [3] 0 0
Approximately 1 year
Secondary outcome [4] 0 0
Duration of response (DOR)
Timepoint [4] 0 0
Approximately 1 year
Secondary outcome [5] 0 0
Incidence of adverse events
Timepoint [5] 0 0
Approximately 1 year
Secondary outcome [6] 0 0
OS in CD30+ participants
Timepoint [6] 0 0
Approximately 2 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2027
Actual
Sample size
Target
Accrual to date
Final
240
Recruitment in Australia
Recruitment state(s)
Othe
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Central Coast Local Health District (Gosford and Wyong Hospitals) - Gosford
Recruitment hospital [3] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 0 0
Hollywood Haematology - Nedlands
Recruitment hospital [5] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
2065 - Saint Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
United States of America
State/province [20] 0 0
Wisconsin
Country [21] 0 0
Belgium
State/province [21] 0 0
Other
Country [22] 0 0
Canada
State/province [22] 0 0
Newfoundland and Labrador
Country [23] 0 0
Canada
State/province [23] 0 0
Nova Scotia
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
Czechia
State/province [26] 0 0
Other
Country [27] 0 0
Denmark
State/province [27] 0 0
Other
Country [28] 0 0
France
State/province [28] 0 0
Other
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
Germany
State/province [30] 0 0
Other
Country [31] 0 0
Italy
State/province [31] 0 0
Other
Country [32] 0 0
Italy
State/province [32] 0 0
Milano
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Other
Country [34] 0 0
Netherlands
State/province [34] 0 0
Other
Country [35] 0 0
Poland
State/province [35] 0 0
Other
Country [36] 0 0
Spain
State/province [36] 0 0
Other
Country [37] 0 0
Switzerland
State/province [37] 0 0
Other
Country [38] 0 0
Taiwan
State/province [38] 0 0
Other
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Other

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Seagen Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04404283
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Seagen Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries