Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies

Phase 2

Completed

Conditions: Acute Myeloid Leukemia
Acute Lymphoid Leukemia
Anemia, Refractory, With Excess of Blasts
Solid Tumors

Interventions: Drug: brentuximab vedotin

Registration Number: NCT01461538

Lead Sponsor: Seagen Inc.

Brief Summary: This is an open-label, multicenter, phase 2 clinical trial to evaluate the antitumor activity of brentuximab vedotin as a single agent in patients with CD30-positive nonlymphomatous malignancies.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 84

Inclusion Criteria

Histologically-confirmed by central review CD30-positive nonlymphomatous malignancy
Have failed, refused, or have been deemed ineligible for standard therapy
Measurable disease
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 or a Karnofsky or Lansky Performance Status score greater than or equal to 70

Exclusion Criteria

Primary diagnosis of lymphoma or central nervous system (CNS) malignancy
History of another primary invasive malignancy that has not been definitively treated or in remission for at least 3 years
Evidence of active cerebral/meningeal disease

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Brentuximab vedotin 1.2 mg/kg	brentuximab vedotin	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by IV infusion
Brentuximab vedotin 1.8 mg/kg	brentuximab vedotin	Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
Brentuximab vedotin 2.4 mg/kg	brentuximab vedotin	Brentuximab vedotin 2.4 mg/kg every 3 weeks by IV infusion

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) by Investigator	Up to approximately 3 years	Percentage of participants who achieved a best response of complete response/remission (CR), CR without hematologic recovery (CRi; leukemia only), or partial remission (PR) per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).

Secondary Outcome Measures

Name	Time	Method
Adverse Events by Severity, Seriousness, and Relationship to Treatment	Up to approximately 3 years	Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-013). 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.
Laboratory Abnormalities >/= Grade 3	Up to approximately 3 years	Counts of study participants with post-baseline laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 4.03. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough)	Up to approximately 3 years
Progression-Free Survival by Kaplan-Meier Analysis	Up to approximately 2 years	Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE)	Up to approximately 3 years
Duration of Complete Response by Kaplan-Meier Analysis	Up to approximately 2 years	Duration of CR, defined as time of initial response until disease progression or death. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi)	Up to approximately 3 years
Incidence of Anti-therapeutic Antibodies (ATA)	Up to approximately 3 years	Counts of participants with post-baseline anti-brentuximab vedotin antibodies. Persistently positive is defined as confirmed ATA in more than 2 post-baseline samples and transiently positive is defined as confirmed ATA in 1 or 2 post-baseline samples.
Duration of Objective Response by Kaplan-Meier Analysis	Up to approximately 2 years	Duration of objective response (CR \[+CRi; leukemia\] + PR), defined as time of initial response until disease progression or death. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).
Complete Remission (CR) Rate by Investigator	Up to approximately 3 years	Percentage of participants who achieved a best response of CR per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).
Brentuximab Vedotin Monomethyl Auristatin E (MMAE) Trough Concentration (Ctrough)	Up to approximately 3 years

Trial Locations

Locations (29): Mayo Clinic Cancer Center
🇺🇸
Jacksonville, Florida, United States
Ocala Oncology Center
🇺🇸
Ocala, Florida, United States
Northwest Cancer Specialists, P.C.
🇺🇸
Tulatin, Oregon, United States
Willamette Valley Cancer and Research / USOR
🇺🇸
Eugene, Oregon, United States
St. Francis Hospital
🇺🇸
Greenville, South Carolina, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
New York Oncology Hematology, P.C.
🇺🇸
Albany, New York, United States
Texas Oncology - Central Austin Cancer Center
🇺🇸
Round Rock, Texas, United States
City of Hope
🇺🇸
Duarte, California, United States
Texas Oncology - Dallas Presbyterian
🇺🇸
Dallas, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸
Fairfax, Virginia, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
Texas Oncology Denton South
🇺🇸
Denton, Texas, United States
Texas Oncology - Waco
🇺🇸
Waco, Texas, United States
Texas Oncology - Medical City Dallas
🇺🇸
Dallas, Texas, United States
Puget Sound Cancer Centers
🇺🇸
Edmonds, Washington, United States
Texas Oncology - Bedford
🇺🇸
Bedford, Texas, United States
Yakima Valley Memorial Hospital / North Star Lodge
🇺🇸
Yakima, Washington, United States
Texas Oncology - Fort Worth 12th Avenue
🇺🇸
Fort Worth, Texas, United States
Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
🇺🇸
Blacksburg, Virginia, United States
Cancer Care Northwest
🇺🇸
Spokane Valley, Washington, United States
Indiana University Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
PMK Medical Group Inc., DBA Ventura County Hematology Oncology Specialists
🇺🇸
Oxnard, California, United States
MD Anderson Cancer Center / University of Texas
🇺🇸
Houston, Texas, United States
MD Anderson Cancer Center Leukemia Group
🇺🇸
Houston, Texas, United States
Cancer Centers of South Texas - HOAST
🇺🇸
San Antonio, Texas, United States
Rocky Mountain Cancer Centers - Aurora
🇺🇸
Aurora, Colorado, United States
Minnesota Oncology Hematology P.A.
🇺🇸
Minneapolis, Minnesota, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States