Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for CD30 Positive Diffuse Large B-cell Lymphoma

NCT02594163 | Terminated Phase 2 Results DMC

• 1 other identifier: SGN35-023
• Study Type: interventional
• Target: 25
• Locations: 7 countries
• Sites: 50

Brief Summary

This is a randomized, open-label, multicenter, Phase 2 clinical trial designed to evaluate the efficacy and safety of brentuximab vedotin in combination with rituximab and bendamustine for the treatment of patients with relapsed or refractory CD30-positive diffuse large B-cell lymphoma (DLBCL) after failure of second-line salvage therapy or as second-line treatment in patients ineligible for autologous stem cell transplant (ASCT).

Conditions

Diffuse Large B-cell Lymphoma Refractory; Follicular B-cell Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of patients who achieve a Complete Response (CR) (including Complete Metabolic Response (CMR)) or Partial Response (PR) (including Partial Metabolic Response (PMR)) as best response to combination therapy on study

  Approximately 1 year

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  Up to 11.8 months

• Complete Remission (CR) Rate

  Approximately 1 year

• Duration of Response (DOR)

  Up to 10.5 months

• Overall Survival (OS)

  Up to 1.5 years

• Number and Severity of Adverse Events (AEs)

  Approximately 1 year

Study Arms (2)

Brentuximab Vedotin

EXPERIMENTAL

Subjects randomized to the brentuximab vedotin arm will receive IV infusions of brentuximab vedotin followed by bendamustine on day 1, and rituximab followed by bendamustine on day 2 of each 21 day cycle.

Drug: Brentuximab Vedotin; Drug: Rituximab; Drug: Bendamustine

Rituximab,Bendamustine control

ACTIVE COMPARATOR

Subjects randomized to the control arm will receive IV infusions of rituximab on day 1 or day 2 and bendamustine on both days 1 and 2 of each 21 day cycle.

Drug: Rituximab; Drug: Bendamustine

Interventions

Brentuximab Vedotin DRUG

Also known as: Adcetris

Brentuximab Vedotin

Rituximab DRUG

Also known as: Rituxan

Brentuximab Vedotin; Rituximab,Bendamustine control

Bendamustine DRUG

Also known as: Treanda

Brentuximab Vedotin; Rituximab,Bendamustine control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with confirmed CD30-positive DLBCL or grade 3b follicular non-Hodgkin lymphoma (NHL).
• Patients must have relapsed or refractory disease following:
• second-line or greater salvage systemic therapy, or
• frontline cytotoxic systemic therapy, for patients who are ineligible for stem cell transplant (SCT).
• Age 18 years and older.
• Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET).
• An Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Acceptable blood test results.
• Females of childbearing potential must have a negative pregnancy test result within 7 days prior to the first dose of study drug.
• Females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of brentuximab vedotin or 12 months following the last dose of rituximab, whichever is later.
• Patients must provide written informed consent.

You may not qualify if:

• History of another invasive malignancy that has not been in remission for at least 1 year. (Exceptions are nonmelanoma skin cancer, curatively treated localized prostate cancer, ductal carcinoma, and cervical carcinoma or a squamous intraepithelial lesion on PAP smear).
• History of progressive multifocal leukoencephalopathy (PML).
• Cerebral/meningeal disease related to the underlying malignancy, unless definitively treated.
• Viral, bacterial, or fungal infection within 2 weeks prior to the first dose of treatment.
• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of study drug.
• Females who are pregnant or breastfeeding.
• Known allergy to any study drug or ingredient contained in the drug formulation of any of the study drugs.
• Known to be positive for hepatitis B. Known to have active hepatitis C infection or on antiviral therapy for hepatitis C within the last 6 months.
• Known to be positive for human immunodeficiency virus (HIV).
• Patients with previous allogeneic stem cell transplant.
• Previous treatment with brentuximab vedotin or bendamustine.
• Intolerable toxicity to prior rituximab therapy.
• Current therapy with other investigational agents.
• Lung disease unrelated to underlying malignancy.
• History of a stroke or transient ischemic attack, unstable angina, myocardial infarction, or cardiac symptoms within 6 months prior to the first dose of treatment.

Sponsors & Collaborators

• Seagen Inc.: lead

Study Sites (50)

City of Hope

Duarte, California, 91010, United States

Location

Sansum Clinic - West Pueblo

Santa Barbara, California, 93105, United States

Location

Good Samaritan Hospital

Torrance, California, 90501, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

Rocky Mountain Cancer Center

Aurora, Colorado, 80012, United States

Location

Kaiser Permanente Oncology

Lonetree, Colorado, 80124, United States

Location

Illinois Cancer Specialists

Niles, Illinois, 60714, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Saint Louis University Cancer Center

St Louis, Missouri, 63110, United States

Location

Saint Francis Cancer Treatment Center

Grand Island, Nebraska, 68803, United States

Location

Hematology and Oncology Associates of Northern New Jersey, P.A.

Morristown, New Jersey, 07962, United States

Location

Willamette Valley Cancer Institute and Research Center

Springfield, Oregon, 97477, United States

Location

Bon Secours Saint Francis Hospital

Greenville, South Carolina, 29607, United States

Location

Greenville Health System Institutional Review Board

Greenville, South Carolina, 29615, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Oncology - Flower Mound

Denton, Texas, 76210, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Oncology and Hematology Associates of Southwest Virginia, Inc.

Roanoke, Virginia, 24014, United States

Location

Virginia Mason Clinical Research

Seattle, Washington, 98101, United States

Location

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, 53188, United States

Location

FN Brno

Brno, 625 00, Czechia

Location

Fakultni Nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultní nemocnice Královské Vinohrady

Prague, 100, Czechia

Location

Centre Hospitalier Regional Universitaire (CHRU) Brest - Hopital Morvan

Brest, France

Location

CHU Côte de Nacre - Caen

Caen, France

Location

Centre Hospitalier des Oudairies

La Roche-sur-Yon, France

Location

Centre Hospitalier du Mans

Le Rocher, 72000, France

Location

CHR Metz

Metz, France

Location

Centre Hospitalier Universitaire de Nantes (CHU Nantes) - Hotel Dieu

Nantes, France

Location

Centre Hospitalier de Perpignan

Perpignan, France

Location

Centre Hospitalier Universitaire (CHU) de Poitier- Hopital de la Miletrie - Hopital Jean Bernard

Poitiers, France

Location

Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou

Rennes, France

Location

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

Bologna, Italy

Location

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, Italy

Location

IRCSS Policlinico San Matteo

Pavia, Italy

Location

Azienda Policlinico Umberto I di Roma

Roma, 00161, Italy

Location

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

A.O Ospadale Di Circolo E Fondazione Macchi

Varese, Italy

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Wojewódzki Szpital Specjalistyczny

Lodz, 93-510, Poland

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Spain

Location

Hospital Universitario La Fe

Valencia, Spain

Location

Hospital Clinico Universitario Lozano Blesa de Zaragoza

Zaragoza, Spain

Location

University Hospital's Birmingham NHS Foundation trust-Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

Location

Liverpool and Broadgreen Hospital

Liverpool, United Kingdom

Location

Maidstone and Tunbridge Wells NHS Trust

Maidstone, United Kingdom

Location

Christie Hospital NHS Foundation Trust

Manchester, United Kingdom

Location

MeSH Terms

Interventions

Brentuximab Vedotin; Rituximab; Bendamustine Hydrochloride

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Seattle Genetics, Inc.

medinfo@seagen.com

855-473-2436

Study Officials

• Thomas Manley, MD

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2015
• First Posted: November 2, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: October 16, 2018
• Results First Posted: October 16, 2018

Record last verified: 2018-09

Locations

IT (6); PL (2); FR (9); CZ (3); ES (4); US (22); GB (4)