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Trial record 1 of 1 for:    C25007
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A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT01990534
Recruitment Status : Active, not recruiting
First Posted : November 21, 2013
Results First Posted : May 5, 2017
Last Update Posted : May 5, 2017
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hodgkin Lymphoma
Intervention Drug: Brentuximab vedotin
Enrollment 60
Recruitment Details Participants took part in the study at 18 investigative sites in Czech Republic, Germany, Malaysia, Poland, Spain, Thailand and Turkey, from 14 March 2014 to data cutoff: 24 March 2016. [24 Months]. Study is ongoing for overall survival.
Pre-assignment Details Participants with a diagnosis of relapsed or refractory Hodgkin Lymphoma were enrolled in 1 treatment group, brentuximab vedotin 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of every 3-week cycle.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Period Title: Overall Study
Started 60
Ongoing 36
Completed 0
Not Completed 60
Reason Not Completed
Death             12
Progressive disease             3
Protocol Violation             1
Withdrawal of Informed Consent             2
Symptomatic Deterioration             1
Withdrawal by Subject             3
Reason Not Specified             2
Progression Free Survival Follow-up             11
Overall Survival Follow-up             25
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Baseline Participants 60
Hide Baseline Analysis Population Description
Safety population included all enrolled participants who received at least 1 dose of brentuximab vedotin.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 60 participants
35.4  (13.83)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants
<65 years 55
≥65 years 5
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Female
24
  40.0%
Male
36
  60.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants
Hispanic or Latino 2
Not Hispanic or Latino 58
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants
White 42
Asian 18
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants
Czech Republic 3
Germany 2
Malaysia 8
Poland 26
Spain 2
Thailand 10
Turkey 9
Baseline Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 60 participants
171.0  (9.66)
Baseline Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 60 participants
70.3  (19.41)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 60 participants
23.864  (5.4085)
[1]
Measure Description: Body Mass Index = weight (kg)/[height (m)^2]
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population included all participants who were enrolled in the study.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
50
(37 to 63)
2.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR is defined as the time in months from the date of first documentation of a CR 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 and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
Time Frame From first documented response until disease progression (Up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were enrolled in the study. All responders were evaluated in this outcome measure. For a participant that has not progressed, DOR is censored at the last response assessment that is SD or better.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 30
Median (95% Confidence Interval)
Unit of Measure: months
4.6
(3.42 to 7.85)
3.Secondary Outcome
Title Progression Free Survival (PFS)
Hide 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 data cut-off: 24 March 2016 (approximate median follow-up 6.9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were enrolled in the study. For a participant that has not progressed and has not died, PFS is censored at the last response assessment that is SD or better.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Median (95% Confidence Interval)
Unit of Measure: months
4.8
(2.96 to 5.32)
4.Secondary Outcome
Title Complete Remission Rate
Hide 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 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were enrolled in the study. In the absence of confirmation of death, survival time is censored at the last date the participant is known to be alive, including study closure.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12
(5 to 23)
5.Secondary Outcome
Title Duration of Complete Remission (CR)
Hide 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 response until disease progression (Up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were enrolled in the study. In the absence of confirmation of death, survival time is censored at the last date the patient is known to be alive, including study closure.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Median (95% Confidence Interval)
Unit of Measure: months
6.1 [1] 
(2.10 to NA)
[1]
Upper limit of CI was not estimable due to the low number of participants with events.
6.Secondary Outcome
Title Overall Survival (OS)
Hide 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 data cut-off: 24 March 2016 (approximate median follow-up 16.6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were enrolled in the study. In the absence of confirmation of death, survival time is censored at the last date the participant is known to be alive, including study closure.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
[1]
Median was not estimable due to the low number of participants with events.
7.Secondary Outcome
Title Percentage of Participants Who Received Stem Cell Transplantation (SCT)
Hide Description [Not Specified]
Time Frame Baseline up to EOS (Up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were enrolled in the study.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: percentage of participants
47
8.Secondary Outcome
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
Hide Description An Adverse Event (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 Serious Adverse Event (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 12.2 months, except for peripheral neuropathy (PN), all PN events will be followed for all changes in severity until resolution to baseline or study closure (Up to 24 months)]
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all enrolled participants who received at least one dose of brentuximab vedotin.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: participants
Any AEs 52
Grade 3 or higher AEs 21
Drug-related AEs 41
Drug-related Grade 3 or higher AEs 11
SAEs 11
Drug-related SAEs 3
9.Secondary Outcome
Title Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs
Hide 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 12.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all enrolled participants who received at least one dose of brentuximab vedotin.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: participants
Neutrophil count decreased 2
Lymphocyte count decreased 1
Alanine aminotransferase increased 2
Aspartate aminotransferase increased 2
Gamma-glutamyltransferase increased 1
Blood thyroid stimulating hormone increased 1
Platelet count decreased 1
Haemoglobin decreased 1
Blood alkaline phosphatase increased 1
Blood lactate dehydrogenase increased 1
10.Secondary Outcome
Title Antibody-drug Conjugate (ADC) Serum Concentrations
Hide 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 12.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. "n" in the categories is the number of participants with data available at the given time-point.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1 Day 1, Pre-Dose (n=59) 0.00  (0.000)
Cycle 1 Day 1, 10 Minutes Post-Dose (n=58) 35504.65  (10226.104)
Cycle 1 Day 2, 24 Hours Post-Dose (n=59) 14517.67  (4481.312)
Cycle 1 Day 15, 336 Hours Post-Dose (n=55) 1410.43  (1946.525)
Cycle 2 Day 1, Pre-Dose (n=52) 526.42  (350.467)
Cycle 2 Day 1, 10 Minutes Post-Dose (n=53) 37118.32  (11678.088)
Cycle 3 Day 1, Pre-Dose (n=49) 2283.30  (7552.322)
Cycle 3 Day 1, 10 Minutes Post-Dose (n=51) 35878.77  (12724.898)
Cycle 3 Day 2, 24 Hours Post-Dose (n=51) 14737.82  (4512.358)
Cycle 3 Day 15, 336 Hours Post-Dose (n=46) 1586.45  (680.955)
Cycle 4 Day 1, Pre-Dose (n=51) 1313.56  (2566.360)
Cycle 4 Day 1, 10 Minutes Post-Dose (n=51) 42915.34  (28221.764)
Cycle 5 Day 1, Pre-Dose (n=43) 1117.01  (637.637)
Cycle 5 Day 1, 10 Minutes Post-Dose (n=41) 36418.77  (10041.935)
Cycle 6 Day 1, Pre-Dose (n=37) 1231.45  (714.383)
Cycle 6 Day 1, 10 Minutes Post-Dose (n=38) 39000.95  (12484.458)
Cycle 7 Day 1, Pre-Dose (n=38) 1285.91  (712.625)
Cycle 7 Day 1, 10 Minutes Post-Dose (n=36) 38814.82  (12471.299)
Cycle 8 Day 1, Pre-Dose (n=22) 1413.98  (782.391)
Cycle 8 Day 1, 10 Minutes Post-Dose (n=24) 39027.22  (9919.251)
Cycle 9 Day 1, Pre-Dose (n=15) 1277.18  (594.603)
Cycle 9 Day 1, 10 Minutes Post-Dose (n=14) 38359.15  (13421.064)
Cycle 10 Day 1, Pre-Dose (n=11) 1498.44  (754.721)
Cycle 10 Day 1, 10 Minutes Post-Dose (n=11) 39890.12  (5376.038)
Cycle 11 Day 1, Pre-Dose (n=9) 1511.35  (461.907)
Cycle 11 Day 1, 10 Minutes Post-Dose (n=9) 39132.17  (6316.541)
Cycle 12 Day 1, Pre-Dose (n=10) 1479.38  (397.816)
Cycle 12 Day 1, 10 Minutes Post-Dose (n=10) 39955.13  (7821.656)
Cycle 13 Day 1, Pre-Dose (n=9) 1423.56  (415.744)
Cycle 13 Day 1, 10 Minutes Post-Dose (n=9) 37609.69  (4563.601)
Cycle 14 Day 1, Pre-Dose (n=8) 1185.62  (422.664)
Cycle 14 Day 1, 10 Minutes Post-Dose (n=8) 38282.29  (10324.023)
Cycle 15 Day 1, Pre-Dose (n=8) 2279.42  (2919.545)
Cycle 15 Day 1, 10 Minutes Post-Dose (n=8) 39068.14  (7981.110)
Cycle 16 Day 1, Pre-Dose (n=8) 1452.23  (429.731)
Cycle 16 Day 1, 10 Minutes Post-Dose (n=8) 38414.73  (9427.315)
End of Treatment (n=49) 1515.30  (6413.367)
11.Secondary Outcome
Title Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Hide 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 12.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. "n" in the categories is the number of participants with data available at the given time-point.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1 Day 1, Pre-Dose (n=58) 0.00  (0.000)
Cycle 1 Day 1, 10 Minutes Post-Dose (n=57) 37329.59  (17724.247)
Cycle 1 Day 2, 24 Hours Post-Dose (n=57) 23248.90  (8228.938)
Cycle 1 Day 15, 336 Hours Post-Dose (n=59) 2791.49  (1413.452)
Cycle 2 Day 1, Pre-Dose (n=56) 1254.86  (774.586)
Cycle 2 Day 1, 10 Minutes Post-Dose (n=54) 39801.87  (12914.837)
Cycle 3 Day 1, Pre-Dose (n=54) 2645.22  (5685.914)
Cycle 3 Day 1, 10 Minutes Post-Dose (n=52) 36461.28  (11144.634)
Cycle 3 Day 2, 24 Hours Post-Dose (n=50) 27071.46  (8069.489)
Cycle 3 Day 15, 336 Hours Post-Dose (n=49) 4033.28  (1760.094)
Cycle 4 Day 1, Pre-Dose (n=52) 2600.73  (2275.881)
Cycle 4 Day 1, 10 Minutes Post-Dose (n=50) 41823.31  (11761.223)
Cycle 5 Day 1, Pre-Dose (n=43) 2690.61  (1254.886)
Cycle 5 Day 1, 10 Minutes Post-Dose (n=42) 43786.57  (15470.979)
Cycle 6 Day 1, Pre-Dose (n=39) 2806.17  (1021.877)
Cycle 6 Day 1, 10 Minutes Post-Dose (n=39) 44936.89  (13827.929)
Cycle 7 Day 1, Pre-Dose (n=38) 3889.94  (6201.351)
Cycle 7 Day 1, 10 Minutes Post-Dose (n=36) 41840.20  (12552.597)
Cycle 8 Day 1, Pre-Dose (n=24) 2932.19  (1089.138)
Cycle 8 Day 1, 10 Minutes Post-Dose (n=24) 42013.77  (12754.334)
Cycle 9 Day 1, Pre-Dose (n=15) 2959.26  (970.811)
Cycle 9 Day 1, 10 Minutes Post-Dose (n=14) 37300.95  (13442.910)
Cycle 10 Day 1, Pre-Dose (n=11) 3189.16  (1484.258)
Cycle 10 Day 1, 10 Minutes Post-Dose (n=11) 38910.05  (6169.552)
Cycle 11 Day 1, Pre-Dose (n=10) 3393.07  (1160.604)
Cycle 11 Day 1, 10 Minutes Post-Dose (n=10) 41238.25  (8081.750)
Cycle 12 Day 1, Pre-Dose (n=10) 3270.44  (965.895)
Cycle 12 Day 1, 10 Minutes Post-Dose (n=10) 37550.64  (12459.906)
Cycle 13 Day 1, Pre-Dose (n=9) 3406.00  (1067.414)
Cycle 13 Day 1, 10 Minutes Post-Dose (n=9) 35694.80  (3720.378)
Cycle 14 Day 1, Pre-Dose (n=8) 2723.01  (1286.457)
Cycle 14 Day 1, 10 Minutes Post-Dose (n=8) 40848.64  (8704.538)
Cycle 15 Day 1, Pre-Dose (n=8) 3111.63  (941.200)
Cycle 15 Day 1, 10 Minutes Post-Dose (n=8) 37091.56  (6644.258)
Cycle 16 Day 1, Pre-Dose (n=8) 3159.38  (1017.679)
Cycle 16 Day 1, 10 Minutes Post-Dose (n=8) 39266.07  (9358.163)
End of Treatment (n=50) 2340.49  (6715.837)
12.Secondary Outcome
Title Monomethyl Auristatin E (MMAE) Serum Concentrations
Hide 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 12.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. "n" in the categories is the number of participants with data available at the given time-point.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 60
Mean (Standard Deviation)
Unit of Measure: pg/mL
Cycle 1 Day 1, Pre-Dose (n=59) 0.78  (5.976)
Cycle 1 Day 1, 10 Minutes Post-Dose (n=58) 591.09  (662.608)
Cycle 1 Day 2, 24 Hours Post-Dose (n=59) 6056.44  (3850.457)
Cycle 1 Day 15, 336 Hours Post-Dose (n=59) 746.12  (1123.502)
Cycle 2 Day 1, Pre-Dose (n=57) 140.11  (111.036)
Cycle 2 Day 1, 10 Minutes Post-Dose (n=55) 539.38  (593.150)
Cycle 3 Day 1, Pre-Dose (n=54) 130.62  (84.152)
Cycle 3 Day 1, 10 Minutes Post-Dose (n=52) 484.88  (701.402)
Cycle 3 Day 2, 24 Hours Post-Dose (n=51) 3076.75  (2330.510)
Cycle 3 Day 15, 336 Hours Post-Dose (n=49) 442.63  (259.360)
Cycle 4 Day 1, Pre-Dose (n=52) 150.95  (123.841)
Cycle 4 Day 1, 10 Minutes Post-Dose (n=52) 497.20  (520.110)
Cycle 5 Day 1, Pre-Dose (n=43) 153.95  (123.337)
Cycle 5 Day 1, 10 Minutes Post-Dose (n=42) 392.50  (320.346)
Cycle 6 Day 1, Pre-Dose (n=39) 158.89  (109.024)
Cycle 6 Day 1, 10 Minutes Post-Dose (n=39) 369.53  (260.871)
Cycle 7 Day 1, Pre-Dose (n=38) 185.91  (147.311)
Cycle 7 Day 1, 10 Minutes Post-Dose (n=37) 363.83  (237.883)
Cycle 8 Day 1, Pre-Dose (n=24) 136.37  (86.947)
Cycle 8 Day 1, 10 Minutes Post-Dose (n=24) 303.43  (202.351)
Cycle 9 Day 1, Pre-Dose (n=15) 142.30  (114.794)
Cycle 9 Day 1, 10 Minutes Post-Dose (n=14) 224.52  (159.833)
Cycle 10 Day 1, Pre-Dose (n=11) 100.78  (57.270)
Cycle 10 Day 1, 10 Minutes Post-Dose (n=11) 253.73  (113.311)
Cycle 11 Day 1, Pre-Dose (n=10) 158.09  (169.963)
Cycle 11 Day 1, 10 Minutes Post-Dose (n=10) 302.60  (175.869)
Cycle 12 Day 1, Pre-Dose (n=10) 175.02  (141.192)
Cycle 12 Day 1, 10 Minutes Post-Dose (n=10) 382.52  (428.255)
Cycle 13 Day 1, Pre-Dose (n=9) 146.76  (61.758)
Cycle 13 Day 1, 10 Minutes Post-Dose (n=9) 258.78  (108.871)
Cycle 14 Day 1, Pre-Dose (n=8) 82.13  (22.661)
Cycle 14 Day 1, 10 Minutes Post-Dose (n=8) 204.29  (121.162)
Cycle 15 Day 1, Pre-Dose (n=8) 133.78  (59.213)
Cycle 15 Day 1, 10 Minutes Post-Dose (n=8) 246.63  (98.399)
Cycle 16 Day 1, Pre-Dose (n=8) 163.39  (114.821)
Cycle 16 Day 1, 10 Minutes Post-Dose (n=8) 264.63  (103.269)
End of Treatment (n=50) 139.72  (220.211)
13.Secondary Outcome
Title Number of Participants With Antitherapeutic Antibodies (ATA)
Hide 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 12.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Safety Population, all enrolled participants who received at least one dose of brentuximab vedotin, with data available for analysis.
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description:
Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Overall Number of Participants Analyzed 56
Measure Type: Number
Unit of Measure: participants
ATA Positive 21
Transient Positive 17
Persistently Positive 4
ATA Titer Low (≤25) 21
ATA Titer High (>25) 0
Time Frame From first dose through 30 days after the last dose of study medication [Up to 12.2 months, except for peripheral neuropathy (PN), all PN events will be followed for all changes in severity until resolution to baseline or study closure (Up to 24 months)]
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Brentuximab Vedotin
Hide Arm/Group Description Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic toxicity, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
All-Cause Mortality
Brentuximab Vedotin
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Brentuximab Vedotin
Affected / at Risk (%)
Total   11/60 (18.33%) 
Cardiac disorders   
Tachycardia  1  1/60 (1.67%) 
Gastrointestinal disorders   
Vomiting  1  1/60 (1.67%) 
General disorders   
General physical health deterioration  1  1/60 (1.67%) 
Immune system disorders   
Serum sickness-like reaction  1  1/60 (1.67%) 
Anaphylactic reaction  1  1/60 (1.67%) 
Infections and infestations   
Bronchitis  1  1/60 (1.67%) 
Pneumonia  1  1/60 (1.67%) 
Device related sepsis  1  1/60 (1.67%) 
Septic shock  1 [1]  1/60 (1.67%) 
Dengue fever  1  1/60 (1.67%) 
Urinary tract infection  1  1/60 (1.67%) 
Viral infection  1  1/60 (1.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Hodgkin's disease  1  1/60 (1.67%) 
Nervous system disorders   
Cerebrovascular accident  1  1/60 (1.67%) 
Psychiatric disorders   
Anxiety  1  1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  1/60 (1.67%) 
Vascular disorders   
Vena cava thrombosis  1  1/60 (1.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
[1]
One treatment-emergent death occurred during treatment with brentuximab 1.8 mg/kg and was related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Brentuximab Vedotin
Affected / at Risk (%)
Total   51/60 (85.00%) 
Blood and lymphatic system disorders   
Anaemia  1  5/60 (8.33%) 
Leukocytosis  1  1/60 (1.67%) 
Leukopenia  1  1/60 (1.67%) 
Neutropenia  1  6/60 (10.00%) 
Thrombocytopenia  1  2/60 (3.33%) 
Cardiac disorders   
Tachycardia  1  2/60 (3.33%) 
Ear and labyrinth disorders   
Ear pain  1  1/60 (1.67%) 
Endocrine disorders   
Autoimmune thyroiditis  1  1/60 (1.67%) 
Eye disorders   
Diplopia  1  1/60 (1.67%) 
Gastrointestinal disorders   
Abdominal pain  1  2/60 (3.33%) 
Constipation  1  2/60 (3.33%) 
Diarrhoea  1  6/60 (10.00%) 
Nausea  1  5/60 (8.33%) 
Toothache  1  1/60 (1.67%) 
Vomiting  1  4/60 (6.67%) 
General disorders   
Asthenia  1  3/60 (5.00%) 
Catheter site inflammation  1  1/60 (1.67%) 
Chest pain  1  1/60 (1.67%) 
Chills  1  1/60 (1.67%) 
Extravasation  1  1/60 (1.67%) 
Fatigue  1  1/60 (1.67%) 
Malaise  1  1/60 (1.67%) 
Oedema  1  1/60 (1.67%) 
Oedema peripheral  1  1/60 (1.67%) 
Pyrexia  1  11/60 (18.33%) 
Soft tissue inflammation  1  1/60 (1.67%) 
Temperature regulation disorder  1  1/60 (1.67%) 
Vaccination site pain  1  1/60 (1.67%) 
Hepatobiliary disorders   
Liver disorder  1  1/60 (1.67%) 
Infections and infestations   
Breast cellulitis  1  1/60 (1.67%) 
Bronchitis  1  3/60 (5.00%) 
Conjunctivitis  1  1/60 (1.67%) 
Coxsackie viral infection  1  1/60 (1.67%) 
Dengue fever  1  1/60 (1.67%) 
Device related infection  1  1/60 (1.67%) 
Herpes zoster  1  1/60 (1.67%) 
Hordeolum  1  1/60 (1.67%) 
Influenza  1  1/60 (1.67%) 
Klebsiella infection  1  1/60 (1.67%) 
Nasopharyngitis  1  2/60 (3.33%) 
Oral herpes  1  2/60 (3.33%) 
Pseudomonas infection  1  1/60 (1.67%) 
Sinusitis  1  1/60 (1.67%) 
Subcutaneous abscess  1  2/60 (3.33%) 
Upper respiratory tract infection  1  5/60 (8.33%) 
Viral infection  1  1/60 (1.67%) 
Injury, poisoning and procedural complications   
Contusion  1  1/60 (1.67%) 
Ligament sprain  1  1/60 (1.67%) 
Procedural pain  1  1/60 (1.67%) 
Investigations   
Alanine aminotransferase increased  1  2/60 (3.33%) 
Aspartate aminotransferase increased  1  2/60 (3.33%) 
Blood alkaline phosphatase increased  1  1/60 (1.67%) 
Blood lactate dehydrogenase increased  1  1/60 (1.67%) 
Blood thyroid stimulating hormone increased  1  1/60 (1.67%) 
Gamma-glutamyltransferase increased  1  1/60 (1.67%) 
Haemoglobin decreased  1  1/60 (1.67%) 
Lymphocyte count decreased  1  1/60 (1.67%) 
Neutrophil count decreased  1  2/60 (3.33%) 
Platelet count decreased  1  1/60 (1.67%) 
Weight decreased  1  1/60 (1.67%) 
Metabolism and nutrition disorders   
Decreased appetite  1  4/60 (6.67%) 
Hyperglycaemia  1  1/60 (1.67%) 
Hyperuricaemia  1  1/60 (1.67%) 
Hypokalaemia  1  3/60 (5.00%) 
Hypomagnesaemia  1  3/60 (5.00%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  4/60 (6.67%) 
Back pain  1  2/60 (3.33%) 
Bone pain  1  2/60 (3.33%) 
Pain in extremity  1  1/60 (1.67%) 
Nervous system disorders   
Autonomic neuropathy  1  1/60 (1.67%) 
Dysgeusia  1  1/60 (1.67%) 
Facial nerve disorder  1  1/60 (1.67%) 
Headache  1  2/60 (3.33%) 
Neuropathy peripheral  1  6/60 (10.00%) 
Paraesthesia  1  3/60 (5.00%) 
Peripheral sensory neuropathy  1  7/60 (11.67%) 
Polyneuropathy  1  5/60 (8.33%) 
Somnolence  1  1/60 (1.67%) 
Psychiatric disorders   
Depression  1  2/60 (3.33%) 
Insomnia  1  1/60 (1.67%) 
Renal and urinary disorders   
Renal tubular disorder  1  1/60 (1.67%) 
Reproductive system and breast disorders   
Genital haemorrhage  1  1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  3/60 (5.00%) 
Dyspnoea  1  1/60 (1.67%) 
Dyspnoea exertional  1  1/60 (1.67%) 
Nasal congestion  1  1/60 (1.67%) 
Upper respiratory tract inflammation  1  1/60 (1.67%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  3/60 (5.00%) 
Dermatitis  1  1/60 (1.67%) 
Dermatitis acneiform  1  1/60 (1.67%) 
Dermatitis allergic  1  1/60 (1.67%) 
Dermatitis contact  1  1/60 (1.67%) 
Erythema  1  1/60 (1.67%) 
Pruritus  1  2/60 (3.33%) 
Pruritus generalised  1  1/60 (1.67%) 
Rash  1  2/60 (3.33%) 
Rash macular  1  1/60 (1.67%) 
Rash maculo-papular  1  1/60 (1.67%) 
Rash papular  1  1/60 (1.67%) 
Rash pruritic  1  1/60 (1.67%) 
Urticaria  1  1/60 (1.67%) 
Vascular disorders   
Haematoma  1  1/60 (1.67%) 
Lymphoedema  1  1/60 (1.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01990534     History of Changes
Other Study ID Numbers: C25007
2013-000232-10 ( EudraCT Number )
U1111-1154-2250 ( Registry Identifier: WHO )
NMRR-13-1246-18099 ( Registry Identifier: NMRR )
REec-2014-0619 ( Registry Identifier: REec )
First Submitted: November 15, 2013
First Posted: November 21, 2013
Results First Submitted: March 23, 2017
Results First Posted: May 5, 2017
Last Update Posted: May 5, 2017