Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies

A Phase 2, Open-label Study of Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Solid Tumors; Acute Lymphoid Leukemia; Anemia, Refractory, With Excess of Blasts
• Intervention / Treatment: Drug: brentuximab vedotin; Drug: brentuximab vedotin; Drug: brentuximab vedotin

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope
    • Oxnard, California, United States, 93030
      • PMK Medical Group Inc., DBA Ventura County Hematology Oncology Specialists
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers - Aurora
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Cancer Center
    • Ocala, Florida, United States, 34471
      • Ocala Oncology Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology P.A.
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology, P.C.
  • Ohio
    • Cleveland, Ohio, United States, 44106-5055
      • University Hospitals Case Medical Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer and Research / USOR
    • Tulatin, Oregon, United States, 97062
      • Northwest Cancer Specialists, P.C.
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • St. Francis Hospital
  • Texas
    • Bedford, Texas, United States, 76022
      • Texas Oncology - Bedford
    • Dallas, Texas, United States, 75230
      • Texas Oncology - Medical City Dallas
    • Dallas, Texas, United States, 75231
      • Texas Oncology - Dallas Presbyterian
    • Denton, Texas, United States, 76210
      • Texas Oncology Denton South
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology - Fort Worth 12th Avenue
    • Houston, Texas, United States, 77030-4003
      • MD Anderson Cancer Center / University of Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center Leukemia Group
    • Round Rock, Texas, United States, 78731
      • Texas Oncology - Central Austin Cancer Center
    • San Antonio, Texas, United States, 78229
      • Cancer Centers of South Texas - HOAST
    • Waco, Texas, United States, 76712
      • Texas Oncology - Waco
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Washington
    • Edmonds, Washington, United States, 98026
      • Puget Sound Cancer Centers
    • Spokane Valley, Washington, United States, 99216
      • Cancer Care Northwest
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital / North Star Lodge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brentuximab vedotin 1.8 mg/kg; Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35; Drug: brentuximab vedotin; 2.4 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35; Drug: brentuximab vedotin; 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion; Other Names: Adcetris; SGN-35
Experimental: Brentuximab vedotin 2.4 mg/kg; Brentuximab vedotin 2.4 mg/kg every 3 weeks by IV infusion	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35; Drug: brentuximab vedotin; 2.4 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35; Drug: brentuximab vedotin; 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion; Other Names: Adcetris; SGN-35
Experimental: Brentuximab vedotin 1.2 mg/kg; Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by IV infusion	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35; Drug: brentuximab vedotin; 2.4 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35; Drug: brentuximab vedotin; 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion; Other Names: Adcetris; SGN-35

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) by Investigator	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).	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission (CR) Rate by Investigator	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).	Up to approximately 3 years
Duration of Objective Response by Kaplan-Meier Analysis	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).	Up to approximately 2 years
Duration of Complete Response by Kaplan-Meier Analysis	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).	Up to approximately 2 years
Progression-Free Survival by Kaplan-Meier Analysis	Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause	Up to approximately 2 years
Adverse Events by Severity, Seriousness, and Relationship to Treatment	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.	Up to approximately 3 years
Laboratory Abnormalities >/= Grade 3	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	Up to approximately 3 years
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi)		Up to approximately 3 years
Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough)		Up to approximately 3 years
Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE)		Up to approximately 3 years
Brentuximab Vedotin Monomethyl Auristatin E (MMAE) Trough Concentration (Ctrough)		Up to approximately 3 years
Incidence of Anti-therapeutic Antibodies (ATA)	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.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Seagen Inc.

Publications and helpful links

General Publications

• Albany C, Einhorn L, Garbo L, Boyd T, Josephson N, Feldman DR. Treatment of CD30-Expressing Germ Cell Tumors and Sex Cord Stromal Tumors with Brentuximab Vedotin: Identification and Report of Seven Cases. Oncologist. 2018 Mar;23(3):316-323. doi: 10.1634/theoncologist.2017-0544. Epub 2017 Dec 8.
• Borate U, Mehta A, Reddy V, Tsai M, Josephson N, Schnadig I. Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin. Leuk Res. 2016 May;44:25-31. doi: 10.1016/j.leukres.2016.02.010. Epub 2016 Feb 27.
• Giannatempo P, Paolini B, Miceli R, Raggi D, Nicolai N, Fare E, Catanzaro M, Biasoni D, Torelli T, Stagni S, Piva L, Mariani L, Salvioni R, Colecchia M, Gianni AM, Necchi A. Persistent CD30 expression by embryonal carcinoma in the treatment time course: prognostic significance of a worthwhile target for personalized treatment. J Urol. 2013 Nov;190(5):1919-24. doi: 10.1016/j.juro.2013.04.057. Epub 2013 Apr 25.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 24, 2011
• First Submitted That Met QC Criteria: October 27, 2011
• First Posted (Estimate): October 28, 2011

Study Record Updates

• Last Update Posted (Estimate): March 4, 2016
• Last Update Submitted That Met QC Criteria: February 5, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Drug Therapy; Immunotherapy; Hematologic Diseases; Antibody-Drug Conjugate; Solid Tumors; Myelodysplastic Syndrome; Antibodies, Monoclonal; Antigens, CD30; Acute Lymphoid Leukemia; Anemia, Refractory, with Excess of Blasts; Monomethyl Auristatin E
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Anemia; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibodies, Monoclonal; Brentuximab Vedotin
• Other Study ID Numbers: SGN35-013