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

Diffuse Large B-cell Lymphoma Refractory Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02594163
• Other study ID #: SGN35-023
• Status: Terminated
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: September 2017

Study information

• Verified date: September 2018
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma Refractory
• Follicular B-cell Non-Hodgkin's Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Brentuximab Vedotin

• Rituximab

• Bendamustine

Locations

Country	Name	City	State
Czechia	FN Brno	Brno
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Králové
Czechia	Fakultní nemocnice Královské Vinohrady	Praha
France	Centre Hospitalier Regional Universitaire (CHRU) Brest - Hopital Morvan	Brest
France	CHU Côte de Nacre - Caen	Caen
France	Centre Hospitalier des Oudairies	La Roche-sur-Yon
France	Centre Hospitalier du Mans	Le Rocher
France	CHR Metz	Metz
France	Centre Hospitalier Universitaire de Nantes (CHU Nantes) - Hotel Dieu	Nantes
France	Centre Hospitalier de Perpignan	Perpignan
France	Centre Hospitalier Universitaire (CHU) de Poitier- Hopital de la Miletrie - Hopital Jean Bernard	Poitiers
France	Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou	Rennes
Italy	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia
Italy	IRCSS Policlinico San Matteo	Pavia
Italy	Azienda Policlinico Umberto I di Roma	Roma
Italy	IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	A.O Ospadale Di Circolo E Fondazione Macchi	Varese
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Wojewódzki Szpital Specjalistyczny	Lódz
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Puerta de Hierro	Majadahonda
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa de Zaragoza	Zaragoza
United Kingdom	University Hospital's Birmingham NHS Foundation trust-Queen Elizabeth Hospital	Birmingham
United Kingdom	Liverpool and Broadgreen Hospital	Liverpool
United Kingdom	Maidstone and Tunbridge Wells NHS Trust	Maidstone
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester
United States	Rocky Mountain Cancer Center	Aurora	Colorado
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Texas Oncology - Flower Mound	Denton	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Saint Francis Cancer Treatment Center	Grand Island	Nebraska
United States	Bon Secours Saint Francis Hospital	Greenville	South Carolina
United States	Greenville Health System Institutional Review Board	Greenville	South Carolina
United States	Kaiser Permanente Oncology	Lonetree	Colorado
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Hematology and Oncology Associates of Northern New Jersey, P.A.	Morristown	New Jersey
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Sansum Clinic - West Pueblo	Santa Barbara	California
United States	Virginia Mason Clinical Research	Seattle	Washington
United States	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon
United States	Good Samaritan Hospital	Torrance	California
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Countries where clinical trial is conducted

United States,  Czechia,  France,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-free Survival (PFS)	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.	Up to 11.8 months
Secondary	Complete Remission (CR) Rate	CRR is the proportion of patients who achieve CR (including Complete Metabolic Response (CMR)) as best response to combination therapy on study.	Approximately 1 year
Secondary	Duration of Response (DOR)	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.	Up to 10.5 months
Secondary	Overall Survival (OS)	OS is defined as the time randomization to death from any cause	Up to 1.5 years
Secondary	Number and Severity of Adverse Events (AEs)	All AEs are included in the summaries, unless treatment-emergent is specified.	Approximately 1 year