Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma

A Phase 4, Open-label, Single-Arm Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma

The purpose of this study is to assess the antitumor efficacy of single-agent brentuximab vedotin 1.8 mg/kg administered intravenously (IV) every 3 weeks, as measured by the overall objective response rate (ORR) in patients with r/r sALCL following at least 1 multiagent chemotherapy regimen (cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone [CHOP] or equivalent multiagent chemotherapy regimens with curative intent).

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Brentuximab vedotin

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • ZNA Stuivenberg
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
• Croatia
  • Rijeka, Croatia, 51000
    • Clinical Hospital Centre Rijeka
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Clinical Hospital Dubrava
• Czechia
  • Brno, Czechia, 625 00
    • Fakultní Nemocnice Brno
  • Olomouc, Czechia, 779 00
    • Fakultni Nemocnice Olomouc
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha 2, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Pecs, Hungary, 7624
    • Pecsi Tudomanyegyetem
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 30-510
    • Malopolskie Centrum Medyczne s.c.
  • Olsztyn, Poland, 10-228
    • SPZOZ MSW zWarminsko-MazurskimCen.Onko.wOlsztynie
  • Warszawa, Poland, 02-781
    • Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto, E.P.E. - Hospital de Santo António
• Romania
  • Brasov, Romania, 500152
    • Policlinica de Diagnostic Rapid SA
  • Bucuresti, Romania, 020125
    • Spitalul Clinic Colentina
  • Bucuresti, Romania, 030171
    • Spitalul Clinic Coltea
  • Targu Mures, Romania, 540042
    • Spitalul Clinic Judetean de Urgenta Targu Mures
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • ICO lHospitalet Hospital Duran i Reynals
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
• Turkey
  • Ankara, Turkey, 06340
    • Ankara University Medical Faculty
  • Denizli, Turkey, 20070
    • Pamukkale Uni. Med. Fac.
  • Istanbul, Turkey, 34200
    • Istanbul Bilim University Medical Fac.
  • Izmir, Turkey, 35040
    • Ege University Medical Faculty
  • Izmir, Turkey, 35340
    • Dokuz Eylul University Faculty of Medicine
  • Kayseri, Turkey, 38039
    • Erciyes University Medical Faculty
• United Kingdom
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • The Christie
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B9 5SS
      • Birmingham Heartlands Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participants age 18 years or older, with relapsed or refractory sALCL who have previously received at least 1 multiagent chemotherapy
• Bidimensional measurable disease
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug, or agree to practice true abstinence
• Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence
• Clinical laboratory values as specified in the study protocol

Exclusion Criteria:

• Previous treatment with brentuximab vedotin.
• Previously received an allogeneic transplant.
• Participants with current diagnosis of primary cutaneous anaplastic large cell lymphoma [ALCL] (participants whose ALCL has transformed to sALCL are eligible).
• Known cerebral/meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy (PML)
• Female participants who are lactating and breastfeeding or pregnant
• Known human immunodeficiency virus (HIV) positive
• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brentuximab Vedotin 1.8 mg/kg; Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.	Drug: Brentuximab vedotin; Brentuximab vedotin IV infusion; Other Names: SGN-35; ADCETRIS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a complete remission (CR) or partial remission (PR) by Independent Review Facility (IRF) response assessment according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.	Up to data cut-off date: 04 May 2021 (Up to approximately 7 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) as Per IRF	DOR was defined as the time between initial response and documented tumor progression in the subset of participants who achieved an objective response, either CR or PR. DOR per IRF was based upon the radiological assessment of measured lesions from an independent review facility. DOR was censored on the date of the last disease assessment documenting absence of progressive disease (PD) for participants who were lost to follow-up, withdrew consent, started a new anticancer therapy other than SCT, or discontinued treatment due to undocumented PD after the last adequate disease assessment.	Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
Progression-free Survival (PFS) as Per IRF	PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. PFS per IRF is based upon the radiological assessment from an independent review facility.	Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
Complete Remission Rate (CRR)	CRR is defined as percentage of participants with CR. CR is defined as the disappearance of all evidence of disease.	Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
Overall Survival (OS)	OS is defined as the time from start of study treatment to date of death due to any cause.	Until death or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
Percentage of Participants Receiving Hematopoietic Stem Cell Transplant (SCT) Following Treatment With Brentuximab Vedotin		Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events, Related Adverse Events and Adverse Events by Severity (Grade 3 or Higher)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. Serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is a medically important event.	From first dose up to 30 days post last dose of study drug (Up to approximately 17 months)
Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion		Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody		Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE)		Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antidrug Antibody (Nab) to Brentuximab Vedotin		Up to 16 cycles (each cycle = 21 days)

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Director: Study Director, Takeda

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2014
• Primary Completion (Actual): May 4, 2021
• Study Completion (Estimated): October 4, 2024

Study Registration Dates

• First Submitted: July 1, 2013
• First Submitted That Met QC Criteria: July 26, 2013
• First Posted (Estimated): July 29, 2013

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Drug Therapy; Immunotherapy; Lymphoma; Relapsed; Refractory; Lymphoma, Non-Hodgkin; Hematologic Diseases; Antibody-Drug Conjugate; Antibodies, Monoclonal; Lymphoma, Large-Cell, Anaplastic; Antigens, CD30; monomethyl auristatin E; Anaplastic Large-cell
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma; Lymphoma, Large-Cell, Anaplastic; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immunoconjugates; Immunotoxins; Brentuximab Vedotin
• Other Study ID Numbers: C25006; 2012-004128-39 (EudraCT Number); U1111-1154-9784 (Registry Identifier: WHO); REec-2014-0649 (Registry Identifier: REec); 13/NI/0072 (Registry Identifier: NRES)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No