Clinical trial NCT02594163: Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for CD30 Positive Diffuse Large B-cell Lymphoma
Official title: A Randomized, Open Label, Phase 2 Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for Relapsed or Refractory CD30-Positive Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma Refractory
Follicular B-cell Non-Hodgkin's Lymphoma
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-01
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Patients with confirmed CD30-positive DLBCL or grade 3b follicular non-Hodgkin lymphoma (NHL).
2. Patients must have relapsed or refractory disease following:

   1. second-line or greater salvage systemic therapy, or
   2. frontline cytotoxic systemic therapy, for patients who are ineligible for stem cell transplant (SCT).
3. Age 18 years and older.
4. Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET).
5. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
6. Acceptable blood test results.
7. Females of childbearing potential must have a negative pregnancy test result within 7 days prior to the first dose of study drug.
8. 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.
9. Patients must provide written informed consent.

Exclusion Criteria:

1. 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).
2. History of progressive multifocal leukoencephalopathy (PML).
3. Cerebral/meningeal disease related to the underlying malignancy, unless definitively treated.
4. Viral, bacterial, or fungal infection within 2 weeks prior to the first dose of treatment.
5. Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of study drug.
6. Females who are pregnant or breastfeeding.
7. Known allergy to any study drug or ingredient contained in the drug formulation of any of the study drugs.
8. 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.
9. Known to be positive for human immunodeficiency virus (HIV).
10. Patients with previous allogeneic stem cell transplant.
11. Previous treatment with brentuximab vedotin or bendamustine.
12. Intolerable toxicity to prior rituximab therapy.
13. Current therapy with other investigational agents.
14. Lung disease unrelated to underlying malignancy.
15. 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.
16. Congestive heart failure.
17. Significant peripheral sensory or motor neuropathy at the start of the study.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Approximately 1 year
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to 11.8 months
measure: Complete Remission (CR) Rate
timeFrame: Approximately 1 year
measure: Duration of Response (DOR)
timeFrame: Up to 10.5 months
measure: Overall Survival (OS)
timeFrame: Up to 1.5 years
measure: Number and Severity of Adverse Events (AEs)
timeFrame: Approximately 1 year
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic - West Pueblo
state: California
city: Torrance
country: United States
facility: Good Samaritan Hospital
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Lonetree
country: United States
facility: Kaiser Permanente Oncology
state: Colorado
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Grand Island
country: United States
facility: Saint Francis Cancer Treatment Center
state: Nebraska
city: Morristown
country: United States
facility: Hematology and Oncology Associates of Northern New Jersey, P.A.
state: New Jersey
city: Springfield
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Greenville
country: United States
facility: Bon Secours Saint Francis Hospital
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Institutional Review Board
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Flower Mound
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Clinical Research
state: Washington
city: Waukesha
country: United States
facility: UW Cancer Center at ProHealth Care
state: Wisconsin
city: Brno
country: Czechia
facility: FN Brno
city: Hradec Králové
country: Czechia
facility: Fakultni Nemocnice Hradec Kralove
city: Praha
country: Czechia
facility: Fakultní nemocnice Královské Vinohrady
city: Brest
country: France
facility: Centre Hospitalier Regional Universitaire (CHRU) Brest - Hopital Morvan
city: Caen
country: France
facility: CHU Côte de Nacre - Caen
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier des Oudairies
city: Le Rocher
country: France
facility: Centre Hospitalier du Mans
city: Metz
country: France
facility: CHR Metz
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (CHU Nantes) - Hotel Dieu
city: Perpignan
country: France
facility: Centre Hospitalier de Perpignan
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire (CHU) de Poitier- Hopital de la Miletrie - Hopital Jean Bernard
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Pavia
country: Italy
facility: IRCSS Policlinico San Matteo
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I di Roma
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
city: Varese
country: Italy
facility: A.O Ospadale Di Circolo E Fondazione Macchi
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Łódź
country: Poland
facility: Wojewódzki Szpital Specjalistyczny
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa de Zaragoza
city: Birmingham
country: United Kingdom
facility: University Hospital's Birmingham NHS Foundation trust-Queen Elizabeth Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool and Broadgreen Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone and Tunbridge Wells NHS Trust
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Foundation Trust
Study officials:
affiliation: Seagen Inc.
name: Thomas Manley, MD
role: STUDY_DIRECTOR
References: