Clinical Trials /

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

NCT04404283

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: SGN35-031
  • NCT ID: NCT04404283

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
Brentuximab vedotinExperimental Arm
RituximabControl Arm
LenalidomideControl Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Experimental ArmExperimentalBrentuximab vedotin + lenalidomide + rituximab
  • Brentuximab vedotin
  • Rituximab
  • Lenalidomide
Control ArmActive ComparatorPlacebo + lenalidomide + rituximab
  • Rituximab
  • Lenalidomide

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFSa per blinded independent central review (BICR) in the ITT population
Time Frame:Up to 1 year
Safety Issue:
Description: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

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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Genetics, Inc.

Last Updated

July 6, 2020