Clinical trial NCT01309789: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Millennium Pharmaceuticals, Inc.
First posted: 2011-03-07
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of adverse events and laboratory abnormalities
timeFrame: Through 1 month after last dose
Secondary outcomes:
measure: Brentuximab vedotin concentration in blood
timeFrame: Through 1 month after last dose
measure: Antitherapeutic antibodies in blood
timeFrame: Through 1 month after last dose
measure: Best clinical response
timeFrame: Through 1 month after last dose
measure: Progression-free survival
timeFrame: Until disease progression or study closure
measure: Overall survival
timeFrame: Every 3 months until death or study closure
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: St. Francis Hospital
state: South Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington Medical Center
state: Washington
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Seagen Inc.
name: Dana Kennedy, PharmD, BCOP
role: STUDY_DIRECTOR
References:
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.
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.