Clinical Trial Results:
A Phase 4, Open-label, Single-Arm Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma
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Summary
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EudraCT number |
2012-004128-39 |
Trial protocol |
GB CZ BE PT ES PL HU HR |
Global end of trial date |
29 Aug 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Oct 2025
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First version publication date |
23 Oct 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C25006
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01909934 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Ave, Lexington, MA, United States, 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Aug 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Aug 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main aim of this study was to determine the antitumor efficacy of single-agent brentuximab vedotin as measured by ORR in participants with relapsed or refractory sALCL following at least 1 multiagent chemotherapy regimen.
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Protection of trial subjects |
Participant signed an informed consent form (ICF) before participating in the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Jan 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
10 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Croatia: 2
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Country: Number of subjects enrolled |
Czechia: 12
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Country: Number of subjects enrolled |
Hungary: 5
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Country: Number of subjects enrolled |
Poland: 8
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Country: Number of subjects enrolled |
Portugal: 3
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Country: Number of subjects enrolled |
Romania: 3
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Country: Number of subjects enrolled |
Spain: 4
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Country: Number of subjects enrolled |
Türkiye: 6
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Country: Number of subjects enrolled |
United Kingdom: 6
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Worldwide total number of subjects |
50
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EEA total number of subjects |
38
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
33
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From 65 to 84 years |
16
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85 years and over |
1
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Recruitment
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Recruitment details |
Participants took part in the study at various investigative sites globally from 23 January 2014 to 29 August 2024. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Participants with a diagnosis of relapsed or refractory systemic anaplastic large cell lymphoma were enrolled to receive brentuximab vedotin 1.8 milligrams per kilogram (mg/kg). | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Brentuximab Vedotin 1.8 mg/kg | ||||||||||||||||||
Arm description |
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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
ADCETRIS
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Investigational medicinal product code |
SGN-35
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Other name |
BRENTUXIMAB VEDOTIN
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Pharmaceutical forms |
Powder for concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Brentuximab vedotin 1.8 mg/kg on Day 1 of each 3-week cycle.
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Baseline characteristics reporting groups
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Reporting group title |
Brentuximab Vedotin 1.8 mg/kg
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Brentuximab Vedotin 1.8 mg/kg
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Reporting group description |
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. | ||
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End point title |
Objective Response Rate (ORR) [1] | ||||||||
End point description |
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. Intent-to-Treat Population included all participants enrolled in the study.
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End point type |
Primary
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End point timeframe |
Up to data cut-off date: 04 May 2021 (Up to approximately 7 years)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analysis was planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Receiving Hematopoietic Stem Cell Transplant (SCT) Following Treatment With Brentuximab Vedotin | ||||||||
End point description |
Intent-to-Treat Population included all participants enrolled in the study.
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End point type |
Secondary
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End point timeframe |
Until disease progression, death, or end of study (Up to approximately 10.7 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
OS is defined as the time from start of study treatment to date of death due to any cause. Intent-to-Treat Population included all participants enrolled in the study. '99999' denotes that upper limit of 95% CI was not estimable due to insufficient number of participants with events.
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End point type |
Secondary
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End point timeframe |
Until disease progression, death, or end of study (Up to approximately 10.7 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free Survival (PFS) as Per IRF | ||||||||
End point description |
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. Intent-to-Treat Population included all participants enrolled in the study. '99999' indicates that upper limit of 95% CI was not estimable due to insufficient number of participants with events up to data cut-off date: 4 May 2021.
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End point type |
Secondary
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End point timeframe |
Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs by Severity (Grade 3 or Higher) | ||||||||||||||||
End point description |
An adverse event (AE): 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 medicinal product. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. Serious TEAEs: 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. Safety population: all participants who received at least 1 dose of brentuximab vedotin.
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End point type |
Secondary
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End point timeframe |
From first dose up to 30 days post last dose of study drug (Up to approximately 1 year)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Duration of Response (DOR) as Per IRF | ||||||||
End point description |
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 stem cell transplant (SCT), or discontinued treatment due to undocumented PD after the last adequate disease assessment. '999' indicates that median and upper limit of confidence interval (CI) were not estimable as most of the responders were censored. Intent-to-Treat Population included all participants enrolled in the study. Only responders were analyzed for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Complete Remission Rate (CRR) as Per IRF | ||||||||
End point description |
CRR is defined as percentage of participants with CR. CR is defined as the disappearance of all evidence of disease. Intent-to-Treat Population included all participants enrolled in the study.
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End point type |
Secondary
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End point timeframe |
Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion | ||||||||||||
End point description |
Pharmacokinetic population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. 'n' denotes number of participants with data available for analyses at the given timepoint.
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End point type |
Secondary
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End point timeframe |
Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody | ||||||||||||
End point description |
Pharmacokinetic population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. 'n' denotes number of participants with data available for analyses at the given timepoint.
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End point type |
Secondary
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End point timeframe |
Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE) | ||||||||||||
End point description |
Pharmacokinetic population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. 'n' denotes number of participants with data available for analyses at the given timepoint.
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End point type |
Secondary
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End point timeframe |
Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antidrug Antibody (Nab) to Brentuximab Vedotin | ||||||||||||
End point description |
Immunogenicity evaluable population included all participants who received at least 1 dose of brentuximab vedotin and had a baseline and at least 1 post-baseline sample available for evaluation for the presence of ATA and Nab. Subjects analysed are participants with data available for analyses at the given timepoint.
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End point type |
Secondary
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End point timeframe |
Up to 16 cycles (each cycle = 21 days)
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All-cause mortality: Throughout the study (Up to approximately 10.7 years); Serious and other adverse events: From first dose up to 30 days post last dose of study drug (up to approximately 1 year)
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Adverse event reporting additional description |
The Safety Population included all participants who received at least 1 dose of brentuximab vedotin.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Brentuximab Vedotin 1.8 mg/kg
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Reporting group description |
Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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13 Mar 2013 |
The following updates were made as per protocol amendment 01: 1. Specified that a minimum of 45 participants were to be treated in this study. 2. Increased the duration of disease status follow-up. 3. Added a criterion excluding participants who had received any investigational products within 4 weeks before the first dose of brentuximab vedotin. |
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27 Aug 2021 |
The following update was made as per protocol amendment 02: 1. Updated the sponsor’s name and legal entity responsible for the study. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
