Clinical Trial Results:
A pivotal study of SGN-35 in treatment of patients with relapsed or refractory Hodgkin Lymphoma (HL) who have previously received autologous stem cell transplant.
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Summary
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EudraCT number |
2008-006034-10 |
Trial protocol |
DE BE IT FR GB |
Global end of trial date |
14 May 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Jul 2016
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First version publication date |
31 Jul 2016
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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 |
SG035-0003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00848926 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
ADCETRIS: SGN-35 | ||
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Sponsors
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Sponsor organisation name |
Seattle Genetics, Inc.
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Sponsor organisation address |
21823 30th Drive SE, Bothell, United States, 98021
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Public contact |
Chief Medical Officer, Seattle Genetics, Inc., 855 473-2436, medinfo@seagen.com
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Scientific contact |
Chief Medical Officer, Seattle Genetics, Inc., 855 473-2436, medinfo@seagen.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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Oct 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Aug 2010
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Global end of trial reached? |
Yes
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Global end of trial date |
14 May 2015
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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 |
To determine the antitumor efficacy of single-agent brentuximab vedotin (1.8 mg/kg administered intravenously every 3 weeks) as measured by the overall objective response rate in patients with relapsed or refractory Hodgkin lymphoma following autologous stem cell transplant
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Protection of trial subjects |
The protocol for this study was designed in accordance with the general ethical principles outlined in the Declaration of Helsinki. The conduct of all aspects of the study, including methods for obtaining informed consent, were also in accordance with principles enunciated in the declaration, the International Conference on Harmonisation (ICH) Good Clinical Practices (GCP), and applicable Food and Drug Administration (FDA) regulations/guidelines set forth in Title 21 CFR Parts 11, 50, 54, 56, and 312. The consent form approved by each IRB/IEC included all elements required by the applicable regional laws and regulations, including a statement that Seattle Genetics, Inc. and authorities had access to patient records. Consent was obtained from all patients before any protocol-required procedures were performed, including any procedure not part of normal patient care.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Feb 2009
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Long term follow-up planned |
No
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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 |
France: 5
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Country: Number of subjects enrolled |
Italy: 3
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Country: Number of subjects enrolled |
Canada: 8
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Country: Number of subjects enrolled |
United States: 86
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Worldwide total number of subjects |
102
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EEA total number of subjects |
8
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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) |
1
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Adults (18-64 years) |
98
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Feb 2009 to Aug 2009 | ||||||||||||||||
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Pre-assignment
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Screening details |
Patients must have had relapsed or refractory HL following autologous stem cell transplant. | ||||||||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Non-randomised - controlled
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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 | ||||||||||||||||
Arm description |
Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Brentuximab vedotin
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Investigational medicinal product code |
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Other name |
ADCETRIS, SGN-35
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Pharmaceutical forms |
Concentrate for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Brentuximab vedotin
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Reporting group description |
Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion | ||
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End point title |
Objective Response Rate by Independent Review Group [1] | ||||||||||
End point description |
Percentage of participants who achieved a best response of complete remission (CR, disappearance of all evidence of disease) or partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
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End point type |
Primary
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End point timeframe |
up to 12 months
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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: The primary efficacy hypothesis was: H0: ORR for SGN-35 (1.8 mg/kg) is <20% versus Ha: ORR for SGN-35 (1.8 mg/kg) is >=20% |
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| Notes [2] - Intention to treat |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Complete Remission Rate by Independent Review Group | ||||||||||
End point description |
Percentage of participants who achieved a best response of CR (disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
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End point type |
Secondary
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End point timeframe |
up to 12 months
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| Notes [3] - Intention to treat |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Duration of Objective Response by Kaplan-Meier Analysis | |||||
End point description |
Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death.
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End point type |
Secondary
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End point timeframe |
up to approximately 4 years
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| No statistical analyses for this end point | ||||||
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End point title |
Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis | |||||
End point description |
Duration of response from start of first objective tumor response (CR or PR) by independent review group to disease progression or death due to any cause in participants with CR.
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End point type |
Secondary
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End point timeframe |
up to approximately 4 years
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| No statistical analyses for this end point | ||||||
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End point title |
Progression-free Survival by Kaplan-Meier Analysis | |||||
End point description |
Time from start of study treatment to disease progression per independent review group or death due to any cause.
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End point type |
Secondary
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End point timeframe |
up to approximately 4 years
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| No statistical analyses for this end point | ||||||
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End point title |
Overall Survival | |||||
End point description |
Time from start of study treatment to date of death due to any cause.
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End point type |
Secondary
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End point timeframe |
up to approximately 6 years
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| No statistical analyses for this end point | ||||||
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End point title |
Adverse Events by Severity, Seriousness, and Relationship to Treatment | ||||||||||||||||||||
End point description |
Counts of participants who had adverse events or treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death). 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.
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End point type |
Secondary
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End point timeframe |
up to 12 months
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| Notes [4] - All participants who received treatment |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Hematology Laboratory Abnormalities >/= Grade 3 | ||||||||||||||||||||
End point description |
Counts of study participants with post-baseline hematology laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
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End point type |
Secondary
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End point timeframe |
up to 12 months
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| Notes [5] - All participants who received treatment |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Chemistry Laboratory Abnormalities >/= Grade 3 | ||||||||||||||||||||||||
End point description |
Counts of study participants with post-baseline chemistry laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 3.0. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category.
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End point type |
Secondary
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End point timeframe |
up to 12 months
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| Notes [6] - All participants who received treatment |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Area Under the Curve | ||||||||
End point description |
Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin
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End point type |
Secondary
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End point timeframe |
3 weeks
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| Notes [7] - All participants who received treatment |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Serum Concentration | ||||||||
End point description |
Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
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End point type |
Secondary
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End point timeframe |
3 weeks
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| Notes [8] - All participants who received treatment |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time of Maximum Serum Concentration | ||||||||||
End point description |
Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
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End point type |
Secondary
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End point timeframe |
3 weeks
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| Notes [9] - All participants who received treatment |
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| No statistical analyses for this end point | |||||||||||
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End point title |
B Symptom Resolution | ||||||||||
End point description |
Percentage of participants with lymphoma-related symptoms (B symptoms: fever, night sweats, or weight loss >10%) at baseline who achieved resolution of all B symptoms at any time during the treatment period.
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End point type |
Other pre-specified
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End point timeframe |
up to 12 months
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| Notes [10] - Participants with B symptoms at baseline |
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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 |
Up to 12 months
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Adverse event reporting additional description |
Treatment-emergent adverse events (TEAEs) defined as newly occurring (not present at baseline) or worsening after first dose of investigational product on Study SG035-0003
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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 |
13
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Reporting groups
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Reporting group title |
Brentuximab vedotin
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Reporting group description |
Brentuximab vedotin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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17 Nov 2008 |
Incorporation of FDA feedback during SPA review.
Clarified that for patients who had bone marrow involvement at baseline, a follow-up bone marrow aspirate and biopsy was required
(within 2 weeks of documentation of response) and must be negative for assessment of a CR. If the follow-up morphology was
indeterminate, the biopsy tissue must be negative by immunohistochemistry or the patient was to be assessed as a PR.
Specified that patients who were later determined to have the incorrect histological cancer type upon central review were to be scored as non-responders for calculating the ORR.
Revised the definition of duration of response such that all deaths occurring prior to disease progression, not just deaths due to HL, were to be considered when determining the end of the response period.
Revised the analysis set definitions such that the intent-to-treat (ITT) analysis set was to include all patients enrolled in the study and was to be used for the primary efficacy analysis. Secondary analyses of all efficacy endpoints were also to be performed in the per-protocol analysis set, defined as all patients who received at least 1 dose of brentuximab vedotin and who had measurable disease at baseline, the correct histological cancer type per central pathology review, and no other major protocol deviations that could potentially affect tumor response. The safety/modified intent-to-treat (mITT) analysis set, defined as all patients who received at least 1 dose of brentuximab vedotin, was to be used for safety analyses, patient demographics and baseline disease characteristics.
Provided rationale as to why no formal interim efficacy or futility analysis was planned for the study. |
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12 Jan 2009 |
Incorporation of further FDA feedback during SPA review. The eligibility criteria were modified as follows:
The time following prior immunotherapy or radioisotopic therapy was extended to 12 weeks so that any therapeutic benefit from these therapies would be realized prior to receiving brentuximab vedotin. This ensured that patients had relapsed or refractory disease prior to enrollment in the study.
A new inclusion criterion was added to define which specific evidence of relapsed or refractory HL was required at the time of study enrollment. |
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03 Oct 2011 |
Added a section regarding the management of suspected PML |
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30 Jan 2012 |
Revised the timing of assessments during the study follow-up period. |
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03 Oct 2013 |
Removed the requirement for CT scanning during the long-term follow-up period. CT scans were only to be done if progression suspected based on clinical signs and symptoms.
Added a long term follow-up questionnaire to be taken by patients who remained in remission. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/22454421 |
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