search
Back to results

A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma

Primary Purpose

Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
brentuximab vedotin
rituximab
Sponsored by
Seagen Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, B-Cell focused on measuring Lymphoma, Large B-Cell, Diffuse, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Lymphoma, Non-Hodgkin, Monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Lymphoma, Lymphoma, B-Cell, Lymphoma, T-Cell

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically-confirmed NHL (DLBCL only for Parts B and C)
  • Relapsed or refractory disease following at least 1 prior systemic therapy
  • Measurable disease of at least 1.5 cm as documented by CT
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

Exclusion Criteria:

  • History of another primary invasive malignancy that has not been in remission for at least 3 years
  • Current diagnosis of systemic or cutaneous anaplastic large cell lymphoma or mycosis fungoides
  • B cell lymphoma previously treated with only single-agent rituximab (for patients receiving brentuximab vedotin only) or corticosteroids as monotherapy
  • Known cerebral/meningeal disease

Sites / Locations

  • University of Alabama at Birmingham
  • City of Hope
  • PMK Medical Group Inc., DBA Ventura County Hematology Oncology Specialists
  • Stanford Cancer Center
  • Rocky Mountain Cancer Centers - Aurora
  • Colorado Blood Cancer Institute
  • Cancer Specialists of North Florida - St. Augustine
  • Emory Winship Cancer Institute
  • Northwestern University
  • University of Chicago
  • Dana-Farber Cancer Institute
  • Minnesota Oncology Hematology P.A.
  • Washington University School of Medicine
  • Comprehensive Cancer Centers of Nevada
  • Hackensack University Medical Center
  • New York Oncology Hematology, P.C.
  • NYU Clinical Cancer Center
  • Columbia University Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Cleveland Clinic, The
  • Willamette Valley Cancer and Research / USOR
  • Medical University of South Carolina
  • St. Francis Hospital
  • Texas Oncology - Medical City Dallas
  • Charles A. Sammons Cancer Center
  • Texas Oncology-Southwest Fort Worth
  • MD Anderson Cancer Center / University of Texas
  • Texas Oncology - Seton Williamson
  • Texas Oncology - Tyler
  • Virginia Cancer Specialists, PC
  • Swedish Cancer Institute Medical Oncology
  • Seattle Cancer Care Alliance / University of Washington Medical Center
  • Northwest Cancer Specialists, P.C.
  • British Columbia Cancer Agency - Vancouver Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Brentuximab vedotin+rituximab

Brentuximab vedotin

Arm Description

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy
Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab
Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.

Secondary Outcome Measures

Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab
Percentage of participants treated with brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Complete Remission (CR) Rate by Investigator
Percentage of participants treated with brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Duration of complete remission (CR) or partial remission (PR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Duration of complete remission (CR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression
Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease), partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites), or stable disease (SD, no new sites and no change in size of previous lesions) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Patients are grouped by CD30-positivity or CD30u (undetectable CD30).
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy
Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1)
End of infusion concentration of ADC following the first dose of brentuximab vedotin
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1)
Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin
Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1)
Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Baseline Soluble CD30 Expression
Serum concentration of soluble CD30 before first dose of brentuximab vedotin

Full Information

First Posted
August 19, 2011
Last Updated
October 14, 2016
Sponsor
Seagen Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01421667
Brief Title
A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma
Official Title
A Phase 2 Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma (NHL)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seagen Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is an open-label, multicenter, phase 2 clinical trial to evaluate the efficacy and safety of brentuximab vedotin as a single agent in patients with CD30-positive non-Hodgkin lymphoma (NHL) (Part A). The study will also evaluate the safety and efficacy of brentuximab vedotin in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Part B) as well as further evaluate correlation of CD30 expression and response in DLBCL (Part C).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell
Keywords
Lymphoma, Large B-Cell, Diffuse, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Lymphoma, Non-Hodgkin, Monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Lymphoma, Lymphoma, B-Cell, Lymphoma, T-Cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
176 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brentuximab vedotin+rituximab
Arm Type
Experimental
Arm Title
Brentuximab vedotin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
brentuximab vedotin
Other Intervention Name(s)
Adcetris; SGN-35
Intervention Description
1.8 mg/kg every 3 weeks by IV infusion
Intervention Type
Drug
Intervention Name(s)
rituximab
Intervention Description
375 mg/m2 every 3 weeks by IV infusion
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy
Description
Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame
Up to approximately 3 years
Title
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab
Description
Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab
Description
Percentage of participants treated with brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame
Up to approximately 3 years
Title
Complete Remission (CR) Rate by Investigator
Description
Percentage of participants treated with brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame
Up to approximately 3 years
Title
Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Description
Duration of complete remission (CR) or partial remission (PR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame
Up to approximately 3 years
Title
Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Description
Duration of complete remission (CR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame
Up to approximately 3 years
Title
Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Description
Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
Time Frame
Up to approximately 3 years
Title
Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression
Description
Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease), partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites), or stable disease (SD, no new sites and no change in size of previous lesions) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Patients are grouped by CD30-positivity or CD30u (undetectable CD30).
Time Frame
Up to 3 years
Title
Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy
Description
Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category.
Time Frame
Up to 3 years
Title
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1)
Description
End of infusion concentration of ADC following the first dose of brentuximab vedotin
Time Frame
1 day
Title
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1)
Description
Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame
3 weeks
Title
Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1)
Description
Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame
3 weeks
Title
Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Description
Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame
3 weeks
Title
Baseline Soluble CD30 Expression
Description
Serum concentration of soluble CD30 before first dose of brentuximab vedotin
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically-confirmed NHL (DLBCL only for Parts B and C) Relapsed or refractory disease following at least 1 prior systemic therapy Measurable disease of at least 1.5 cm as documented by CT Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Exclusion Criteria: History of another primary invasive malignancy that has not been in remission for at least 3 years Current diagnosis of systemic or cutaneous anaplastic large cell lymphoma or mycosis fungoides B cell lymphoma previously treated with only single-agent rituximab (for patients receiving brentuximab vedotin only) or corticosteroids as monotherapy Known cerebral/meningeal disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Corinna Palanca-Wessels, MD, PhD
Organizational Affiliation
Seagen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
PMK Medical Group Inc., DBA Ventura County Hematology Oncology Specialists
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5821
Country
United States
Facility Name
Rocky Mountain Cancer Centers - Aurora
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80012
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Cancer Specialists of North Florida - St. Augustine
City
St. Augustine
State/Province
Florida
ZIP/Postal Code
32086
Country
United States
Facility Name
Emory Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Minnesota Oncology Hematology P.A.
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
New York Oncology Hematology, P.C.
City
Albany
State/Province
New York
ZIP/Postal Code
12206
Country
United States
Facility Name
NYU Clinical Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Cleveland Clinic, The
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Willamette Valley Cancer and Research / USOR
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
St. Francis Hospital
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Texas Oncology - Medical City Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Texas Oncology-Southwest Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76132
Country
United States
Facility Name
MD Anderson Cancer Center / University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4003
Country
United States
Facility Name
Texas Oncology - Seton Williamson
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78665
Country
United States
Facility Name
Texas Oncology - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Virginia Cancer Specialists, PC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Swedish Cancer Institute Medical Oncology
City
Edmonds
State/Province
Washington
ZIP/Postal Code
98026
Country
United States
Facility Name
Seattle Cancer Care Alliance / University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Northwest Cancer Specialists, P.C.
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98684
Country
United States
Facility Name
British Columbia Cancer Agency - Vancouver Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
24652992
Citation
Horwitz SM, Advani RH, Bartlett NL, Jacobsen ED, Sharman JP, O'Connor OA, Siddiqi T, Kennedy DA, Oki Y. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014 May 15;123(20):3095-100. doi: 10.1182/blood-2013-12-542142. Epub 2014 Mar 20.
Results Reference
result
PubMed Identifier
25573987
Citation
Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. doi: 10.1182/blood-2014-09-598763. Epub 2015 Jan 8.
Results Reference
result
PubMed Identifier
27868471
Citation
Bartlett NL, Smith MR, Siddiqi T, Advani RH, O'Connor OA, Sharman JP, Feldman T, Savage KJ, Shustov AR, Diefenbach CS, Oki Y, Palanca-Wessels MC, Uttarwar M, Li M, Yang J, Jacobsen ED. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leuk Lymphoma. 2017 Jul;58(7):1607-1616. doi: 10.1080/10428194.2016.1256481. Epub 2016 Nov 20.
Results Reference
derived

Learn more about this trial

A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma

We'll reach out to this number within 24 hrs