Clinical trial NCT01716806: A Study of Brentuximab Vedotin With Hodgkin Lymphoma (HL) and CD30-expressing Peripheral T-cell Lymphoma (PTCL)
Official title: A Phase 2 Open-label Study of Brentuximab Vedotin in Front-line Therapy of Hodgkin Lymphoma (HL) an dCD30-expressing Peripheral T-cell Lymphoma (PTCL) in Older Patients or Patients With Significant Comorbidities Ineligible for Standard Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Disease
Peripheral T Cell Lymphoma
Keywords: Antibody-Drug Conjugate
Antibodies, Monoclonal
Hematologic Diseases
Hodgkin Disease
Antigens, CD30
Lymphoma
monomethylauristatin E
Drug Therapy
CD30-expression
PTCL
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2012-10-30
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will study brentuximab vedotin to find out whether it is an effective treatment for Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL). Participants in this study will be older or will have other conditions that make them unable to have standard chemotherapy treatment. The study will look at brentuximab vedotin alone and combined with other drugs.

Detailed description: This study is designed to evaluate the efficacy and tolerability of brentuximab vedotin as monotherapy and in combination with other agents as frontline therapy. There are 6 parts of the study. The population to be studied includes treatment-naïve patients with classical Hodgkin lymphoma (HL) or treatment-naïve patients with CD30-expressing peripheral T-cell lymphoma (PTCL).

Eligibility criteria: Inclusion Criteria:

* Parts A, B, C, and D: 60 years of age or older
* Treatment-naive patients with histopathological diagnosis of classical Hodgkin lymphoma (Parts A, B, C, D, and E)
* Treatment-naive patients with CD30-expressing PTCL (Part F)
* Ineligible for or have declined initial conventional combination chemotherapy for HL (Parts A, B, C, and D)
* Unsuitable or unfit for initial conventional combination chemotherapy for HL (Part E) or CD30-expressing PTCL due to the presence of comorbidity-factors, as documented by:

  * A CIRS score of 10 or greater
  * Requiring assistance with or dependence on other for any instrumental activities of daily living (IADLs)
* Measurable disease of at least 1.5 cm as documented by radiographic technique
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3 (Parts, A, B, C, E, and F) or less than or equal to 2 (Part D)

Exclusion Criteria:

* Symptomatic neurologic disease compromising IADLs or requiring medication
* History of progressive multifocal leukoencephalopathy
* Grade 3 or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of brentuximab vedotin
* Concurrent use of other investigational agents
* Chemotherapy, radiotherapy, biologics, and/or other treatment with immunotherapy not completed 4 weeks prior to first dose of study drug
* History of another malignancy within 1 year before first dose of study drug (Parts E and F only)
* Part D only:

  * Received any prior immune-oncology therapy
  * History of known or suspected autoimmune disease
  * Prior allogeneic stem cell transplant
  * History of cerebral vascular event within 6 months of first dose of study drug
  * Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicology
  * Known history of pancreatitis
* Parts D, E, and F only:

  * Known cerebral/meningeal disease related to the underlying malignancy
  * Systemic treatment with corticosteroids or other immunosuppressive medications within 1 week of enrollment

Primary outcomes:
measure: Objective Response Rate (ORR) According to the Revised Response Criteria for Malignant Lymphoma (Parts A, B, and C)
timeFrame: Up to 81 months
measure: ORR According to the Lugano Classification Revised Staging System for Nodal Non-Hodgkin and Hodgkin Lymphomas (Lugano Criteria) and the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Part D)
timeFrame: Up to 60 months
measure: ORR According to Modified Lugano Criteria Per Blinded Independent Central Review (BICR) (Parts E and F)
timeFrame: Up to 31 months
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to 122 months
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Up to 30 months
measure: Complete Response Rate
timeFrame: Up to 81 months
measure: Duration of Complete Response
timeFrame: Up to 81 months
measure: Duration of Objective Response
timeFrame: Up to 81 months
measure: Progression-free Survival
timeFrame: Up to 83 months
measure: Disease Control Rate
timeFrame: Up to 81 months
measure: ORR According to Lugano Criteria Per BICR (Parts E and F)
timeFrame: Up to 31 months
measure: B Symptom Resolution Rate
timeFrame: Up to 42 weeks
measure: Number of Participants With Brentuximab Vedotin Antitherapeutic Antibodies (ATA)
timeFrame: Up to 30 months
measure: Number of Participants With Nivolumab Antitherapeutic Antibodies (ATA) (Part D Only)
timeFrame: Up to 30 months
measure: Overall Survival (Parts E and F Only)
timeFrame: Up to 44 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama - Mitchell Cancer Institute
state: Alabama
city: Anchorage
country: United States
facility: Alaska Urological Institute
state: Alaska
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center / University of Arizona
state: Arizona
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Burbank
country: United States
facility: Providence St Joseph Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Pomona
country: United States
facility: Wilshire Oncology Medical Group Inc.
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: Trinity
country: United States
facility: Florida Cancer Affiliates
state: Florida
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: Sandy Springs
country: United States
facility: Georgia Cancer Specialists / Northside Hospital Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists / Advocate Lutheran General Hospital
state: Illinois
city: Bethesda
country: United States
facility: American Oncology Networks LLC
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology P.A.
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Morristown
country: United States
facility: Morristown Medical Center/ Carol G. Simon Cancer Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center / University of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Columbus
country: United States
facility: James Cancer Hospital / Ohio State University
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Tigard
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Arlington
country: United States
facility: Arlington Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology - Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Presbyterian Cancer Center Dallas
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Denton South
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth 12th Avenue
state: Texas
city: Houston
country: United States
facility: Houston Methodist Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Longview
country: United States
facility: Texas Oncology - Longview
state: Texas
city: McAllen
country: United States
facility: Texas Oncology - McAllen
state: Texas
city: Round Rock
country: United States
facility: Texas Oncology - Seton Williamson
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Salem
country: United States
facility: Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
state: Virginia
city: Winchester
country: United States
facility: Shenandoah Oncology P.C.
state: Virginia
city: Seattle
country: United States
facility: Benaroya Research Institute/Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta / Cross Cancer Institute
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de L'Est de l'lle de Montreal / installation Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital, McGill University Health Centre
state: Quebec
Study officials:
affiliation: Seagen Inc.
name: Robert Sims, MD
role: STUDY_DIRECTOR
References:
citation: Friedberg JW, Forero-Torres A, Bordoni RE, Cline VJM, Patel Donnelly D, Flynn PJ, Olsen G, Chen R, Fong A, Wang Y, Yasenchak CA. Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged >/=60 years with HL. Blood. 2017 Dec 28;130(26):2829-2837. doi: 10.1182/blood-2017-06-787200. Epub 2017 Oct 16.
citation: Forero-Torres A, Holkova B, Goldschmidt J, Chen R, Olsen G, Boccia RV, Bordoni RE, Friedberg JW, Sharman JP, Palanca-Wessels MC, Wang Y, Yasenchak CA. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015 Dec 24;126(26):2798-804. doi: 10.1182/blood-2015-06-644336. Epub 2015 Sep 16.
citation: Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW, Matous JV, Shustov AR, Smith SE, Zain J, O'Meara MM, Fanale MA. Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. Leuk Lymphoma. 2014 Oct;55(10):2328-34. doi: 10.3109/10428194.2013.876496. Epub 2014 Feb 24.