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

• ClinicalTrials.gov Identifier: NCT04404283
• Recruitment Status: Recruiting
• First Posted: May 27, 2020
• Last Update Posted: February 2, 2021
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Tracking Information

• First Submitted Date: May 21, 2020
• First Posted Date: May 27, 2020
• Last Update Posted Date: February 2, 2021
• Actual Study Start Date: August 20, 2020
• Estimated Primary Completion Date: November 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 13, 2020)

• PFS per blinded independent central review (BICR) in the ITT population [ Time Frame: Up to 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.
• PFS per BICR in the CD30-positive population [ Time Frame: Up to 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.

Original Primary Outcome Measures (submitted: May 21, 2020)

• PFSa per blinded independent central review (BICR) in the ITT population [ Time Frame: Up to 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.
• PFS per BICR in the CD30-positive population [ Time Frame: Up to 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.

Current Secondary Outcome Measures (submitted: May 21, 2020)

• Objective response rate (ORR) per BICR [ Time Frame: Up to 1 year ]
  Proportion of subjects with complete response (CR) or partial response (PR) according to the Lugano Criteria for Response Assessment (Cheson 2014).
• Overall survival (OS) in the ITT population [ Time Frame: Up to 18 months ]
  me from the date of randomization to date of death due to any cause.
• OS in the CD30+ population [ Time Frame: Up to 18 months ]
  Time from the date of randomization to date of death due to any cause.
• Complete response (CR) rate [ Time Frame: Up to 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.
• Duration of objective response [ Time Frame: Up to 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.
• Incidence of adverse events [ Time Frame: Up to 1 year ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL
• 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)

Brief Summary

This study is being done to see if adding brentuximab vedotin helps two drugs work better to treat patients with diffuse large B-cell lymphoma (DLBCL). Participants in this study will have DLBCL that has come back or not gotten better with treatment.

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diffuse Large B-cell Lymphoma

Intervention

• Drug: Brentuximab vedotin
  1.2 mg/kg administered via intravenous infusion every 3 weeks
• Drug: Rituximab
  375 mg/m^2 administered via intravenous infusion on Cycle 1 Day 1. 1400 mg via subcutaneous injection permitted every 3 weeks from Cycle 2 Day 1 through end of treatment.
• Drug: Lenalidomide
  20 mg orally daily
• Other: Placebo
  Administered via intravenous infusion every 3 weeks

Study Arms

• Experimental: Experimental Arm
  Brentuximab vedotin + lenalidomide + rituximab
  Interventions:

  • Drug: Brentuximab vedotin
  • Drug: Rituximab
  • Drug: Lenalidomide
• Active Comparator: Control Arm
  Placebo + lenalidomide + rituximab
  Interventions:

  • Drug: Rituximab
  • Drug: Lenalidomide
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 21, 2020): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: November 30, 2022 (Final data collection date for primary outcome measure)

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.

• 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, or insurance 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.
• Participants must be registered into the mandatory lenalidomide REMS® program and be willing to comply with its requirements. Per standard lenalidomide REMS® program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the lenalidomide REMS® program.

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
• Participants who are breastfeeding
• Known hypersensitivity to any study drug or excipient contained in the drug formulation of the study drugs
• Known to be positive for hepatitis B by surface antigen expression. Known to be positive for hepatitis C infection (positive by polymerase chain reaction [PCR] or on antiviral therapy for hepatitis C within the last 6 months). Participants who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks.

• Participants with previous allogeneic HSCT if they meet either of the following criteria:

  1. <100 days from HSCT
  2. Active acute or chronic graft-versus-host disease (GVHD) or receiving immunosuppressive therapy as treatment for or prophylaxis against GVHD
• Previous treatment with brentuximab vedotin or lenalidomide

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04404283
• Other Study ID Numbers: SGN35-031
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Seagen Inc.
• Study Sponsor: Seagen Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Robert Sims, MD; Seagen Inc.

• PRS Account: Seagen Inc.
• Verification Date: January 2021