Back to resultsA Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma
Primary Purpose
Hodgkin Lymphoma
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Brentuximab Vedotin
Sponsored by
About this trial
This is an interventional treatment trial for Hodgkin Lymphoma focused on measuring Lymphoma, Hodgkin, Relapsed, Refractory, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Additional Relevant MeSH terms:, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Hodgkin, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, B-Cell, Lymphoma, T-Cell, Immunologic Factors, Physiological Effects of Drugs, Pharmacologic Actions
Eligibility Criteria
Inclusion Criteria:
Each participant must meet all of the following inclusion criteria to be enrolled in the study:
- Male or female participants 18 years or older, with relapsed or refractory classical Hodgkin lymphoma (HL), who have previously received at least 1 prior systemic chemotherapeutic regimen
Not suitable for stem cell transplantation (SCT) or multiagent chemotherapy, according to 1 of the following criteria:
- Disease progression within 90 days of the earliest date of complete remission (CR) or complete remission unconfirmed (CRu) after the end of treatment with multiagent chemotherapeutic regimens and/or radiotherapy
- Progressive disease during frontline multiagent chemotherapy
- Disease relapse after treatment with at least 2 chemotherapeutic regimens, including any salvage treatments
- Bidimensional measurable disease
- An Eastern Cooperative Oncology Group (ECOG) performance status score 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, 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:
Participants who meet any of the following exclusion criteria are not to be enrolled in the study:
- Previous treatment with brentuximab vedotin
- Previously received an autologous stem cell transplantation (ASCT) or alloSCT
- Known cerebral/meningeal disease, including signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML), or any history of PML.
- Female participants who are lactating and breastfeeding or pregnant.
- Known human immunodeficiency virus (HIV).
- Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.
- Grade 2 or higher peripheral neuropathy.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Brentuximab Vedotin 1.8 mg/kg
Arm Description
Brentuximab vedotin 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 in every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose could be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR)
Objective response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using 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.
Secondary Outcome Measures
Duration of Response (DOR)
DOR is defined as the time in months from the date of first documentation of a CR or PR response to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
Progression Free Survival (PFS)
PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first.
Complete Remission Rate
Complete remission rate is defined as percentage of participants with CR per IRF response assessment based on IWG criteria are reported. CR is defined as the disappearance of all evidence of disease.
Duration of Complete Remission
Duration of CR is defined as the time from the date of first documentation of a CR or to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
Overall Survival (OS)
OS is the time in months from start of study treatment to date of death due to any cause.
Percentage of Participants Who Received Hematopoietic SCT
Number of Participants With Adverse Events (AEs), Drug-Related AEs, Grade 3 or Higher AEs, Serious Adverse Events (SAEs), Drug-Related SAEs and Grade 3 or Higher SAEs
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE a serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. AEs Grade 3 and higher are severe.
Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs
Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
Antibody-drug Conjugate (ADC) Serum Concentrations
Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Blood samples were collected and tested for conjugated and unconjugated antibodies.
Monomethyl Auristatin E (MMAE) Serum Concentrations
Blood samples were collected and tested for MMAE serum concentrations.
Number of Participants With Antitherapeutic Antibodies (ATA)
Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-Baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-Baseline confirmed ATA positive responses) and neutralizing ATA (nATA) status. The confirmed ATA-positive samples were assessed for ATA titer and delineated into having high or low titers.
Full Information
NCT ID
NCT01990534
First Posted
November 15, 2013
Last Updated
March 10, 2021
Sponsor
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01990534
Brief Title
A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma
Official Title
A Single-arm Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma Who Are Not Suitable for Stem Cell Transplantation or Multiagent Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
March 14, 2014 (Actual)
Primary Completion Date
March 24, 2016 (Actual)
Study Completion Date
March 12, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase 4, single-arm, open-label, multicenter study is designed to evaluate the efficacy and safety of brentuximab vedotin as a single agent in adult participants with histologically confirmed CD30+ relapsed or refractory classical Hodgkin Lymphoma who have not received a prior stem cell transplantation (SCT) and are considered to be not suitable for SCT or multiagent chemotherapy at the time of study entry.
Detailed Description
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat people who have relapsed or refractory Hodgkin Lymphoma. This study will look at the overall response of people who took brentuximab vedotin.
The study will enroll 60 patients. Participants received:
• Brentuximab vedotin 1.8 mg/kg
This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 6 to 7 years. Participants will make multiple visits to the clinic, and will be contacted by telephone every 3 months for 18 months after the end of treatment (EOT) for follow-up assessment of overall survival and then every 6 months until death, study closure, or 5 years after enrollment of the last participant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma
Keywords
Lymphoma, Hodgkin, Relapsed, Refractory, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases, Additional Relevant MeSH terms:, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Hodgkin, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, B-Cell, Lymphoma, T-Cell, Immunologic Factors, Physiological Effects of Drugs, Pharmacologic Actions
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Brentuximab Vedotin 1.8 mg/kg
Arm Type
Experimental
Arm Description
Brentuximab vedotin 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 in every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose could be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Intervention Type
Drug
Intervention Name(s)
Brentuximab Vedotin
Other Intervention Name(s)
SGN-35, ADCETRIS
Intervention Description
Brentuximab vedotin IV infusion
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Objective response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using 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.
Time Frame
Baseline until disease progression, death or end of study (EOS) (Up to 24 months)
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
DOR is defined as the time in months from the date of first documentation of a CR or PR response to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
Time Frame
From first documented complete or partial remission until disease progression (Up to 24 months)
Title
Progression Free Survival (PFS)
Description
PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first.
Time Frame
Baseline until disease progression, death or end of treatment (EOT), and then every 3 months up to approximately 6 years
Title
Complete Remission Rate
Description
Complete remission rate is defined as percentage of participants with CR per IRF response assessment based on IWG criteria are reported. CR is defined as the disappearance of all evidence of disease.
Time Frame
Baseline until disease progression, death or EOS (Up to approximately 6 years)
Title
Duration of Complete Remission
Description
Duration of CR is defined as the time from the date of first documentation of a CR or to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
Time Frame
From first documented complete remission until disease progression (up to approximately 6 years)
Title
Overall Survival (OS)
Description
OS is the time in months from start of study treatment to date of death due to any cause.
Time Frame
Every 3 months for 18 months after EOT, thereafter, every 6 months until the sooner of death, study closure, or 5 years after enrollment of the last participant (up to approximately 6 years)
Title
Percentage of Participants Who Received Hematopoietic SCT
Time Frame
Baseline up to EOS (up to approximately 6 years)
Title
Number of Participants With Adverse Events (AEs), Drug-Related AEs, Grade 3 or Higher AEs, Serious Adverse Events (SAEs), Drug-Related SAEs and Grade 3 or Higher SAEs
Description
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE a serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. AEs Grade 3 and higher are severe.
Time Frame
From first dose through 30 days after the last dose of study medication (Up to 24 months)
Title
Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs
Description
Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
Time Frame
From the first dose through 30 days after the last dose of study medication (Up to 24 months)
Title
Antibody-drug Conjugate (ADC) Serum Concentrations
Description
Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
Time Frame
Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months)
Title
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Description
Blood samples were collected and tested for conjugated and unconjugated antibodies.
Time Frame
Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months)
Title
Monomethyl Auristatin E (MMAE) Serum Concentrations
Description
Blood samples were collected and tested for MMAE serum concentrations.
Time Frame
Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months)
Title
Number of Participants With Antitherapeutic Antibodies (ATA)
Description
Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-Baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-Baseline confirmed ATA positive responses) and neutralizing ATA (nATA) status. The confirmed ATA-positive samples were assessed for ATA titer and delineated into having high or low titers.
Time Frame
Day 1 of every 3-week cycle up to 16 cycles and EOT (Up to 24 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Each participant must meet all of the following inclusion criteria to be enrolled in the study:
Male or female participants 18 years or older, with relapsed or refractory classical Hodgkin lymphoma (HL), who have previously received at least 1 prior systemic chemotherapeutic regimen
Not suitable for stem cell transplantation (SCT) or multiagent chemotherapy, according to 1 of the following criteria:
Disease progression within 90 days of the earliest date of complete remission (CR) or complete remission unconfirmed (CRu) after the end of treatment with multiagent chemotherapeutic regimens and/or radiotherapy
Progressive disease during frontline multiagent chemotherapy
Disease relapse after treatment with at least 2 chemotherapeutic regimens, including any salvage treatments
Bidimensional measurable disease
An Eastern Cooperative Oncology Group (ECOG) performance status score 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, 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:
Participants who meet any of the following exclusion criteria are not to be enrolled in the study:
Previous treatment with brentuximab vedotin
Previously received an autologous stem cell transplantation (ASCT) or alloSCT
Known cerebral/meningeal disease, including signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML), or any history of PML.
Female participants who are lactating and breastfeeding or pregnant.
Known human immunodeficiency virus (HIV).
Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.
Grade 2 or higher peripheral neuropathy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
City
Praha
State/Province
Prague
Country
Czechia
City
Brno
Country
Czechia
City
Heidelberg
State/Province
Baden Wuerttemberg
Country
Germany
City
Koeln
Country
Germany
City
Georgetown
State/Province
Penang
Country
Malaysia
City
Ampang
State/Province
Selangor
Country
Malaysia
City
Kuala Lumpur
Country
Malaysia
City
Gdansk
Country
Poland
City
Krakow
Country
Poland
City
Warszawa
Country
Poland
City
Pamplona
State/Province
Navarra
Country
Spain
City
Madrid
Country
Spain
City
Bangkoknoi
State/Province
Bangkok
Country
Thailand
City
Patumwan
State/Province
Bangkok
Country
Thailand
City
Ratchathewi
State/Province
Bangkok
Country
Thailand
City
Izmir
State/Province
Bornova
Country
Turkey
City
Ankara
Country
Turkey
City
Izmir
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://vivli.org/ourmember/takeda/
Learn more about this trial
A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma
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