Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for CD30 Positive Diffuse Large B-cell Lymphoma
- Conditions
- Follicular B-cell Non-Hodgkin's LymphomaDiffuse Large B-cell Lymphoma Refractory
- Interventions
- Registration Number
- NCT02594163
- Lead Sponsor
- Seagen Inc.
- 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).
- Detailed Description
Patients will be randomized in a 1:1 manner to receive rituximab plus bendamustine with or without brentuximab vedotin. Patients who respond to combination treatment containing brentuximab vedotin and do not experience excessive toxicity may receive additional single-agent brentuximab vedotin following combination treatment, for up to an additional 10 cycles (up to 16 total cycles of treatment).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 25
-
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.
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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.
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Patients must provide written informed consent.
- 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.
- Congestive heart failure.
- Significant peripheral sensory or motor neuropathy at the start of the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Brentuximab Vedotin Rituximab 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. Brentuximab Vedotin Brentuximab Vedotin 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. Rituximab,Bendamustine control Rituximab 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. Brentuximab Vedotin Bendamustine 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. Rituximab,Bendamustine control Bendamustine 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.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Approximately 1 year 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
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Up to 11.8 months PFS is defined as the time from randomization to disease progression/relapse, receipt of subsequent lymphoma chemotherapy other than the components of the study treatment regimen, or death from any cause, whichever occurs first.
Complete Remission (CR) Rate Approximately 1 year CRR is the proportion of patients who achieve CR (including Complete Metabolic Response (CMR)) as best response to combination therapy on study.
Duration of Response (DOR) Up to 10.5 months DOR is defined as the time from first observation of response to disease progression/relapse, receipt of subsequent lymphoma chemotherapy other than the components of the study treatment regimen, or death from any cause, whichever occurs first.
Overall Survival (OS) Up to 1.5 years OS is defined as the time randomization to death from any cause
Number and Severity of Adverse Events (AEs) Approximately 1 year All AEs are included in the summaries, unless treatment-emergent is specified.
Trial Locations
- Locations (50)
Good Samaritan Hospital
🇺🇸Torrance, California, United States
Saint Francis Cancer Treatment Center
🇺🇸Grand Island, Nebraska, United States
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
Greenville Health System Institutional Review Board
🇺🇸Greenville, South Carolina, United States
Bon Secours Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
CHU Côte de Nacre - Caen
🇫🇷Caen, France
Fakultní nemocnice Královské Vinohrady
🇨🇿Praha, Czechia
Centre Hospitalier Universitaire de Nantes (CHU Nantes) - Hotel Dieu
🇫🇷Nantes, France
Wojewódzki Szpital Specjalistyczny
🇵🇱Łódź, Poland
IRCSS Policlinico San Matteo
🇮🇹Pavia, Italy
Liverpool and Broadgreen Hospital
🇬🇧Liverpool, United Kingdom
A.O Ospadale Di Circolo E Fondazione Macchi
🇮🇹Varese, Italy
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
University Hospital's Birmingham NHS Foundation trust-Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Hospital Clinico Universitario Lozano Blesa de Zaragoza
🇪🇸Zaragoza, Spain
Maidstone and Tunbridge Wells NHS Trust
🇬🇧Maidstone, United Kingdom
Centre Hospitalier Regional Universitaire (CHRU) Brest - Hopital Morvan
🇫🇷Brest, France
Centre Hospitalier du Mans
🇫🇷Le Rocher, France
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
City of Hope
🇺🇸Duarte, California, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Springfield, Oregon, United States
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Spain
IRCCS Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Italy
FN Brno
🇨🇿Brno, Czechia
Virginia Mason Clinical Research
🇺🇸Seattle, Washington, United States
Azienda Policlinico Umberto I di Roma
🇮🇹Roma, Italy
Fakultni Nemocnice Hradec Kralove
🇨🇿Hradec Králové, Czechia
Sansum Clinic - West Pueblo
🇺🇸Santa Barbara, California, United States
Kaiser Permanente Oncology
🇺🇸Lonetree, Colorado, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Rocky Mountain Cancer Center
🇺🇸Aurora, Colorado, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Hematology and Oncology Associates of Northern New Jersey, P.A.
🇺🇸Morristown, New Jersey, United States
Texas Oncology - Flower Mound
🇺🇸Denton, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Centre Hospitalier des Oudairies
🇫🇷La Roche-sur-Yon, France
Oncology and Hematology Associates of Southwest Virginia, Inc.
🇺🇸Roanoke, Virginia, United States
CHR Metz
🇫🇷Metz, France
Centre Hospitalier Universitaire (CHU) de Poitier- Hopital de la Miletrie - Hopital Jean Bernard
🇫🇷Poitiers, France
Centre Hospitalier de Perpignan
🇫🇷Perpignan, France
Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
🇫🇷Rennes, France
Azienda Ospedaliera Spedali Civili di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Italy
Christie Hospital NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Saint Louis University Cancer Center
🇺🇸Saint Louis, Missouri, United States