A Phase 2 Open Label Trial of Brentuximab Vedotin (SGN-35) for Systemic Anaplastic Large Cell Lymphoma
Primary Purpose
Lymphoma, Large-Cell, Anaplastic, Lymphoma, Non-Hodgkin
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
brentuximab vedotin
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Large-Cell, Anaplastic focused on measuring Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic, monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Patients with relapsed or refractory systemic ALCL who have previously received front line chemotherapy.
- Documented anaplastic lymphoma kinase (ALK) status.
- Histologically-confirmed CD30-positive disease; tissue from the most recent post diagnostic biopsy of relapsed/refractory disease must be available for confirmation of CD30 expression via slides or tumor block.
- Fluorodeoxyglucose-avid and measurable disease of at least 1.5 cm as documented by both positron emission tomography and spiral computed tomography.
- Received any previous autologous stem cell transplant at least 12 weeks (3 months) prior.
- At US sites, patients greater than or equal to 12 years of age may be enrolled. At non-US sites, patients must be greater than or equal to 18 years of age.
Exclusion Criteria:
- Previous treatment with brentuximab vedotin.
- Previously received an allogeneic transplant.
- Patients with current diagnosis of primary cutaneous ALCL (patients who have transformed to systemic ALCL are eligible).
- Known cerebral/meningeal disease.
Sites / Locations
- University of Alabama at Birmingham
- Stanford University Medical Center
- Rocky Mountain Cancer Centers
- University of Miami Sylvester Comprehensive Cancer Center
- Northwestern University
- Karmanos Cancer Institute / Wayne State University
- Mayo Clinic Rochester
- Washington University School of Medicine
- Memorial Sloan Kettering Cancer Center
- Weill Cornell Medical College
- Nationwide Children's Hospital
- Oregon Health & Science University
- Baylor Sammons Cancer Center / Texas Oncology
- MD Anderson Cancer Center / University of Texas
- University of Washington
- UZ Gasthuisberg
- B.C Cancer Agency
- Princess Margaret Hospital
- Institut Paoli Calmettes
- Hospital Saint Louis
- Centre Henri Becquerel
- Christie Hospital NHS
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Brentuximab vedotin
Arm Description
Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion
Outcomes
Primary Outcome Measures
Objective Response Rate by Independent Review Group
Percentage of participants 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.
Secondary Outcome Measures
Complete Remission Rate by Independent Review Group
Percentage of participants who achieved a best response of CR (disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Duration of Objective Response by Kaplan-Meier Analysis
Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death.
Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis
Duration of response from start of first objective tumor response (CR or PR) by independent review group to disease progression or death due to any cause in participants with CR.
Progression-free Survival by Kaplan-Meier Analysis
Time from start of study treatment to disease progression per independent review group or death due to any cause.
Overall Survival
Time from start of study treatment to date of death due to any cause.
Adverse Events by Severity, Seriousness, and Relationship to Treatment
Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death). 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.
Hematology Laboratory Abnormalities >/= Grade 3
Counts of study participants with post-baseline hematology laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
Chemistry Laboratory Abnormalities >/= Grade 3
Counts of study participants with post-baseline chemistry laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
Area Under the Curve
Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin
Maximum Serum Concentration
Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time of Maximum Serum Concentration
Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Full Information
NCT ID
NCT00866047
First Posted
March 19, 2009
Last Updated
February 2, 2017
Sponsor
Seagen Inc.
Collaborators
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00866047
Brief Title
A Phase 2 Open Label Trial of Brentuximab Vedotin (SGN-35) for Systemic Anaplastic Large Cell Lymphoma
Official Title
A Phase 2 Study of SGN-35 in Treatment of Patients With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma (ALCL)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seagen Inc.
Collaborators
Millennium Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single-arm, open-label, multicenter, clinical trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) as a single agent in patients with relapsed or refractory ALCL.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Large-Cell, Anaplastic, Lymphoma, Non-Hodgkin
Keywords
Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic, monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Brentuximab vedotin
Arm Type
Experimental
Arm Description
Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion
Intervention Type
Drug
Intervention Name(s)
brentuximab vedotin
Other Intervention Name(s)
SGN-35, ADCETRIS
Intervention Description
1.8 mg/kg every 3 weeks by IV infusion
Primary Outcome Measure Information:
Title
Objective Response Rate by Independent Review Group
Description
Percentage of participants 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 12 months
Secondary Outcome Measure Information:
Title
Complete Remission Rate by Independent Review Group
Description
Percentage of participants who achieved a best response of CR (disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame
up to 12 months
Title
Duration of Objective Response by Kaplan-Meier Analysis
Description
Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death.
Time Frame
up to approximately 3 years
Title
Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis
Description
Duration of response from start of first objective tumor response (CR or PR) by independent review group to disease progression or death due to any cause in participants with CR.
Time Frame
up to approximately 3 years
Title
Progression-free Survival by Kaplan-Meier Analysis
Description
Time from start of study treatment to disease progression per independent review group or death due to any cause.
Time Frame
up to approximately 3 years
Title
Overall Survival
Description
Time from start of study treatment to date of death due to any cause.
Time Frame
up to approximately 7 years
Title
Adverse Events by Severity, Seriousness, and Relationship to Treatment
Description
Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death). 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 12 months
Title
Hematology Laboratory Abnormalities >/= Grade 3
Description
Counts of study participants with post-baseline hematology laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
Time Frame
up to 12 months
Title
Chemistry Laboratory Abnormalities >/= Grade 3
Description
Counts of study participants with post-baseline chemistry laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
Time Frame
up to 12 months
Title
Area Under the Curve
Description
Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin
Time Frame
3 weeks
Title
Maximum Serum Concentration
Description
Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame
3 weeks
Title
Time of Maximum Serum Concentration
Description
Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame
3 weeks
Other Pre-specified Outcome Measures:
Title
B Symptom Resolution
Description
Percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss >10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period.
Time Frame
up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with relapsed or refractory systemic ALCL who have previously received front line chemotherapy.
Documented anaplastic lymphoma kinase (ALK) status.
Histologically-confirmed CD30-positive disease; tissue from the most recent post diagnostic biopsy of relapsed/refractory disease must be available for confirmation of CD30 expression via slides or tumor block.
Fluorodeoxyglucose-avid and measurable disease of at least 1.5 cm as documented by both positron emission tomography and spiral computed tomography.
Received any previous autologous stem cell transplant at least 12 weeks (3 months) prior.
At US sites, patients greater than or equal to 12 years of age may be enrolled. At non-US sites, patients must be greater than or equal to 18 years of age.
Exclusion Criteria:
Previous treatment with brentuximab vedotin.
Previously received an allogeneic transplant.
Patients with current diagnosis of primary cutaneous ALCL (patients who have transformed to systemic ALCL are eligible).
Known cerebral/meningeal disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dana Kennedy, PharmD
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
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Karmanos Cancer Institute / Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
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
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Baylor Sammons Cancer Center / Texas Oncology
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
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
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
UZ Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
B.C Cancer Agency
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Hospital Saint Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Christie Hospital NHS
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22614995
Citation
Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Yang Y, Sievers EL, Kennedy DA, Shustov A. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2190-6. doi: 10.1200/JCO.2011.38.0402. Epub 2012 May 21.
Results Reference
result
PubMed Identifier
28974506
Citation
Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Fenton K, Huebner D, Pinelli JM, Kennedy DA, Shustov A. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017 Dec 21;130(25):2709-2717. doi: 10.1182/blood-2017-05-780049. Epub 2017 Oct 3. Erratum In: Blood. 2018 Jul 26;132(4):458-459.
Results Reference
derived
Links:
URL
http://www.ALCL.com
Description
Related Info
Learn more about this trial
A Phase 2 Open Label Trial of Brentuximab Vedotin (SGN-35) for Systemic Anaplastic Large Cell Lymphoma
We'll reach out to this number within 24 hrs