A Phase 1 Study of Brentuximab Vedotin Given Sequentially and Combined With Multi-Agent Chemotherapy for CD30-Positive Mature T-Cell and NK-Cell Neoplasms
Primary Purpose
Lymphoma, Large-Cell, Anaplastic, Lymphoma, NK-cell, Lymphoma, T-cell
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
brentuximab vedotin
cyclophosphamide
brentuximab vedotin
prednisone
cyclophosphamide
doxorubicin
doxorubicin
prednisone
vincristine
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Large-Cell, Anaplastic focused on measuring Antibodies, Monoclonal, Antibody-Drug Conjugate, Antigens, CD30, Drug Therapy, Hematologic Diseases, Lymphoma, monomethyl auristatin E, Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-cell, Lymphoma, NK-cell
Eligibility Criteria
Inclusion Criteria:
- Treatment-naive CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma
- Measurable disease of at least 1.5 cm
- ECOG performance status less than or equal to 2
Exclusion Criteria:
- Known cerebral/meningeal disease, including history of progressive multifocal leukoencephalopathy
- Current diagnosis of primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, Sezary syndrome or other primary cutaneous lymphomas; extranodal NK/T-cell lymphoma, nasal type
- History of another primary malignancy that has not been in remission for at least 3 years
- Left ventricular ejection fraction <45% or symptomatic cardiac disease, or myocardial infarction within the past 12 months
- Viral, bacterial, or fungal infection within two weeks prior to the first dose of brentuximab vedotin
- Known human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus positive status
Sites / Locations
- UAB Comprehensive Cancer Center
- City of Hope National Medical Center
- Stanford Cancer Center
- Washington University School of Medicine
- Memorial Sloan Kettering Cancer Center
- Fox Chase Cancer Center
- St. Francis Hospital
- MD Anderson Cancer Center / University of Texas
- Seattle Cancer Care Alliance / University of Washington Medical Center
- Christie Hospital NHS Foundation Trust
- Southampton General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
1
2
3 Brentuximab vedotin/CH-P
Arm Description
Sequential
Combination
Combination
Outcomes
Primary Outcome Measures
Incidence of adverse events and laboratory abnormalities
Secondary Outcome Measures
Brentuximab vedotin concentration in blood
Antitherapeutic antibodies in blood
Best clinical response
Progression-free survival
Overall survival
Full Information
NCT ID
NCT01309789
First Posted
February 25, 2011
Last Updated
June 27, 2017
Sponsor
Seagen Inc.
Collaborators
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01309789
Brief Title
A Phase 1 Study of Brentuximab Vedotin Given Sequentially and Combined With Multi-Agent Chemotherapy for CD30-Positive Mature T-Cell and NK-Cell Neoplasms
Official Title
A Phase 1 Study of Brentuximab Vedotin Administered Sequentially and Concurrently With Multi-Agent Chemotherapy as Front-Line Therapy in Patients With CD30-Positive Mature T-Cell and NK-Cell Neoplasms, Including Systemic Anaplastic Large Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
February 28, 2017 (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
No
5. Study Description
Brief Summary
The purpose of this study is to assess the safety profile of brentuximab vedotin sequentially and in combination with multi-agent chemotherapy in front-line treatment for CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma. It is a phase 1, open-label, dose escalation study in three arms designed to define the MTD, PK, immunogenicity, and anti-tumor activity of brentuximab vedotin in sequence and in combination with multi-agent front-line chemotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Large-Cell, Anaplastic, Lymphoma, NK-cell, Lymphoma, T-cell
Keywords
Antibodies, Monoclonal, Antibody-Drug Conjugate, Antigens, CD30, Drug Therapy, Hematologic Diseases, Lymphoma, monomethyl auristatin E, Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-cell, Lymphoma, NK-cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Sequential
Arm Title
2
Arm Type
Experimental
Arm Description
Combination
Arm Title
3 Brentuximab vedotin/CH-P
Arm Type
Experimental
Arm Description
Combination
Intervention Type
Drug
Intervention Name(s)
brentuximab vedotin
Other Intervention Name(s)
SGN-35
Intervention Description
1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-2 and if response, Cycles 9-16)
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
750 mg/m2 IV every 3 weeks (Cycles 3-8)
Intervention Type
Drug
Intervention Name(s)
brentuximab vedotin
Other Intervention Name(s)
SGN-35
Intervention Description
1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-6 and if response, Cycles 7-16)
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
100 mg daily PO on Days 1-5 every 3 weeks (Cycles 3-8)
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
750 mg/m2 IV every 3 weeks (Cycles 1-6)
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Intervention Description
50 mg/m2 IV every 3 weeks (Cycles 3-8)
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Intervention Description
50 mg/m2 IV every 3 weeks (Cycles 1-6)
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
100 mg daily PO on Days 1-5 every 3 weeks (Cycles 1-6)
Intervention Type
Drug
Intervention Name(s)
vincristine
Intervention Description
1.4 mg/m2 IV every 3 weeks (Cycles 3-8)
Primary Outcome Measure Information:
Title
Incidence of adverse events and laboratory abnormalities
Time Frame
Through 1 month after last dose
Secondary Outcome Measure Information:
Title
Brentuximab vedotin concentration in blood
Time Frame
Through 1 month after last dose
Title
Antitherapeutic antibodies in blood
Time Frame
Through 1 month after last dose
Title
Best clinical response
Time Frame
Through 1 month after last dose
Title
Progression-free survival
Time Frame
Until disease progression or study closure
Title
Overall survival
Time Frame
Every 3 months until death or study closure
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Treatment-naive CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma
Measurable disease of at least 1.5 cm
ECOG performance status less than or equal to 2
Exclusion Criteria:
Known cerebral/meningeal disease, including history of progressive multifocal leukoencephalopathy
Current diagnosis of primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, Sezary syndrome or other primary cutaneous lymphomas; extranodal NK/T-cell lymphoma, nasal type
History of another primary malignancy that has not been in remission for at least 3 years
Left ventricular ejection fraction <45% or symptomatic cardiac disease, or myocardial infarction within the past 12 months
Viral, bacterial, or fungal infection within two weeks prior to the first dose of brentuximab vedotin
Known human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus positive status
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dana Kennedy, PharmD, BCOP
Organizational Affiliation
Seagen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UAB Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Washington University School of Medicine
City
Saint 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
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
St. Francis Hospital
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29601
Country
United States
Facility Name
MD Anderson Cancer Center / University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4000
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
Christie Hospital NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25135998
Citation
Fanale MA, Horwitz SM, Forero-Torres A, Bartlett NL, Advani RH, Pro B, Chen RW, Davies A, Illidge T, Huebner D, Kennedy DA, Shustov AR. Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. J Clin Oncol. 2014 Oct 1;32(28):3137-43. doi: 10.1200/JCO.2013.54.2456. Epub 2014 Aug 18.
Results Reference
result
PubMed Identifier
29507077
Citation
Fanale MA, Horwitz SM, Forero-Torres A, Bartlett NL, Advani RH, Pro B, Chen RW, Davies A, Illidge T, Uttarwar M, Lee SY, Ren H, Kennedy DA, Shustov AR. Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas. Blood. 2018 May 10;131(19):2120-2124. doi: 10.1182/blood-2017-12-821009. Epub 2018 Mar 5.
Results Reference
derived
Learn more about this trial
A Phase 1 Study of Brentuximab Vedotin Given Sequentially and Combined With Multi-Agent Chemotherapy for CD30-Positive Mature T-Cell and NK-Cell Neoplasms
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