Study of Brentuximab Vedotin Combined With Bendamustine in Patients With Hodgkin Lymphoma

A Phase 1/2 Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Brentuximab Vedotin in Combination With Bendamustine in Patients With Relapsed or Refractory Hodgkin Lymphoma (HL)

The purpose of this study is to assess safety and efficacy of brentuximab vedotin in combination with bendamustine in patients with relapsed or refractory Hodgkin lymphoma. It is an open-label, 2-stage study designed to determine the recommended dose level of bendamustine in combination with brentuximab vedotin. The study will assess the safety profile of the combination treatment and determine what proportion of patients achieve a complete remission.

Study Overview

• Status: Completed
• Conditions: Hodgkin Disease
• Intervention / Treatment: Drug: brentuximab vedotin; Drug: bendamustine

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
    • Whittier, California, United States, 90603
      • Oncology Institute of Hope & Innovation, The
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • University Of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10022
      • Columbia University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Jewish Hospital, The
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University / University Hospitals Case Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital / Bon Secours
  • Texas
    • Dallas, Texas, United States, 75246
      • Charles A. Sammons Cancer Center / Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histopathological diagnosis of classical Hodgkin lymphoma
• Failed standard front-line therapy
• Measurable disease of at least 1.5 cm as documented by radiographic technique
• Eastern Cooperative Oncology Group performance status less than or equal to 2

Exclusion Criteria:

• Received prior salvage therapy, including radiotherapy
• Chemotherapy, radiotherapy, biologics, and/or other treatment with immunotherapy not completed 4 weeks prior to first dose of study drug
• Concurrent use of other investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Brentuximab Vedotin + Bendamustine; Brentuximab vedotin 1.8 mg/kg every 3 weeks for up to 16 cycles by IV infusion and bendamustine 90 mg/m2 on Days 1 and 2 every 3 weeks by IV infusion for up to 6 cycles	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35; Drug: bendamustine; 90 mg/m2 on Days 1 and 2 of 3-week cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission Rate	Complete remission rate among all subjects (Phase 1 and 2 combined) treated at the dose level selected for Phase 2. Complete remission (CR) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma is a disappearance of all evidence of disease.	Up to 4.6 months
Incidence of Adverse Events (AEs)	All AEs reported after initiation of treatment and pre-existing conditions that worsen after initiation of treatment will be considered treatment-emergent AEs (TEAEs). All AEs will be coded by system organ class, MedDRA preferred term, and severity grade using NCI CTCAE V4.03. All recorded AEs will be included in the data listings.	Up to 13.8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-limiting Toxicities	Incidence of dose-limiting toxicity (DLT) was evaluated in an initial safety cohort of 10 patients who were followed for protocol-defined DLT events until Cycle 2 Day 1.	Up to 3 weeks; first cycle of therapy through the first day of Cycle 2
Overall Best Response Rate	Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease), partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites), stable disease (SD, failure to obtain a complete or partial response or progressive disease), or progressive disease (PD, any new lesion or increase by 50% or more of previously involved sites from nadir) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma	Up to 4.6 months
Duration of Response	The time from first observation of remission to disease progression/relapse or death from any cause, whichever occurs first.	Up to 47.8 months
Progression-free Survival	The time from first dose of study medication to first documentation of disease progression/relapse, or to death due to any cause, whichever occurs first.	Up to 49 months

Collaborators and Investigators

• Sponsor: Seagen Inc.

Publications and helpful links

General Publications

• LaCasce AS, Bociek RG, Sawas A, Caimi P, Agura E, Matous J, Ansell SM, Crosswell HE, Islas-Ohlmayer M, Behler C, Cheung E, Forero-Torres A, Vose J, O'Connor OA, Josephson N, Wang Y, Advani R. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood. 2018 Jul 5;132(1):40-48. doi: 10.1182/blood-2017-11-815183. Epub 2018 Apr 27.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): February 20, 2018

Study Registration Dates

• First Submitted: June 6, 2013
• First Submitted That Met QC Criteria: June 6, 2013
• First Posted (ESTIMATE): June 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2019
• Last Update Submitted That Met QC Criteria: January 24, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy; Immunotherapy; Lymphoma; Hematologic Diseases; Antibody-Drug Conjugate; Antibodies, Monoclonal; Antigens, CD30; Hodgkin Disease; monomethylauristatin E
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Bendamustine Hydrochloride; Brentuximab Vedotin
• Other Study ID Numbers: SGN35-016