A Phase 2 Open Label Trial of Brentuximab Vedotin (SGN-35) for Systemic Anaplastic Large Cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Seattle Genetics, Inc.
ClinicalTrials.gov Identifier:
NCT00866047
First received: March 19, 2009
Last updated: June 30, 2014
Last verified: June 2014
Results First Received: September 15, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Lymphoma, Large-Cell, Anaplastic
Lymphoma, Non-Hodgkin
Intervention: Drug: brentuximab vedotin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrollment period: Jun 2009 - May 2010

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion

Participant Flow for 2 periods

Period 1:   Treatment Period
    Brentuximab Vedotin  
STARTED     58  
COMPLETED     3 [1]
NOT COMPLETED     55  
Progressive disease                 13  
Adverse Event                 14  
Physician Decision                 14  
Withdrawal by Subject                 5  
Continuing on treatment                 9  
[1] Number who completed 16 cycles of treatment

Period 2:   Follow-up Period
    Brentuximab Vedotin  
STARTED     43 [1]
COMPLETED     12 [2]
NOT COMPLETED     31  
Continuing in follow-up                 31  
[1] All participants were to be followed after treatment
[2] Completed survival follow-up due to death



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Baseline Measures
    Brentuximab Vedotin  
Number of Participants  
[units: participants]
  58  
Age, Customized  
[units: years]
Median ( Full Range )
  52.0  
  ( 14 to 76 )  
Gender  
[units: participants]
 
Female     25  
Male     33  
Race (NIH/OMB)  
[units: participants]
 
American Indian or Alaska Native     0  
Asian     1  
Native Hawaiian or Other Pacific Islander     0  
Black or African American     7  
White     48  
More than one race     0  
Unknown or Not Reported     2  
Eastern Cooperative Oncology Group Performance Status [1]
[units: participants]
 
0     19  
1     38  
2     1  
3-5     0  
ALK Status [2]
[units: participants]
 
Positive     16  
Negative     42  
[1]

0 = Normal activity

  1. = Symptoms but ambulatory
  2. = In bed <50% of the time
  3. = In bed >50% of the time
  4. = 100% bedridden
  5. = Dead
[2] Immunophenotype status with respect to anaplastic lymphoma kinase (ALK) protein



  Outcome Measures
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1.  Primary:   Objective Response Rate by Independent Review Group   [ Time Frame: up to 12 months ]

Measure Type Primary
Measure Title Objective Response Rate by Independent Review Group
Measure 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.
Time Frame up to 12 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Objective Response Rate by Independent Review Group  
[units: percent of participants]
Number ( 95% Confidence Interval )
  86  
  ( 74.6 to 93.9 )  

No statistical analysis provided for Objective Response Rate by Independent Review Group



2.  Secondary:   Complete Remission Rate by Independent Review Group   [ Time Frame: up to 12 months ]

Measure Type Secondary
Measure Title Complete Remission Rate by Independent Review Group
Measure 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.
Time Frame up to 12 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Complete Remission Rate by Independent Review Group  
[units: percent of participants]
Number ( 95% Confidence Interval )
  57  
  ( 43.2 to 69.8 )  

No statistical analysis provided for Complete Remission Rate by Independent Review Group



3.  Secondary:   Duration of Objective Response by Kaplan-Meier Analysis   [ Time Frame: up to 17.5 months ]

Measure Type Secondary
Measure Title Duration of Objective Response by Kaplan-Meier Analysis
Measure Description Duration of objective response (CR + PR) by independent review group, defined as time of initial response until disease progression or death.
Time Frame up to 17.5 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants with objective response among the intention to treat population

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  50  
Duration of Objective Response by Kaplan-Meier Analysis  
[units: months]
Median ( 95% Confidence Interval )
  12.6  
  ( 5.7 to NA ) [1]
[1] Insufficient number of events to estimate upper bound

No statistical analysis provided for Duration of Objective Response by Kaplan-Meier Analysis



4.  Secondary:   Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis   [ Time Frame: up to 17.5 months ]

Measure Type Secondary
Measure Title Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis
Measure 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.
Time Frame up to 17.5 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants with complete remission among the intention to treat population

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  33  
Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis  
[units: months]
Median ( 95% Confidence Interval )
  13.2  
  ( 10.8 to NA ) [1]
[1] Insufficient number of events to estimate upper bound

No statistical analysis provided for Duration of Objective Response in Participants With Complete Remission by Kaplan-Meier Analysis



5.  Secondary:   Progression-free Survival by Kaplan-Meier Analysis   [ Time Frame: up to 17.5 months ]

Measure Type Secondary
Measure Title Progression-free Survival by Kaplan-Meier Analysis
Measure Description Time from start of study treatment to disease progression per independent review group or death due to any cause.
Time Frame up to 17.5 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Progression-free Survival by Kaplan-Meier Analysis  
[units: months]
Median ( 95% Confidence Interval )
  13.3  
  ( 6.9 to NA ) [1]
[1] Insufficient number of events to estimate upper bound

No statistical analysis provided for Progression-free Survival by Kaplan-Meier Analysis



6.  Secondary:   Overall Survival   [ Time Frame: up to 17.5 months ]

Measure Type Secondary
Measure Title Overall Survival
Measure Description Time from start of study treatment to date of death due to any cause.
Time Frame up to 17.5 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Overall Survival  
[units: months]
Median ( 95% Confidence Interval )
  NA  
  ( 14.6 to NA ) [1]
[1] Insufficient number of events to estimate median and upper bound

No statistical analysis provided for Overall Survival



7.  Secondary:   Adverse Events by Severity, Seriousness, and Relationship to Treatment   [ Time Frame: up to 12 months ]

Measure Type Secondary
Measure Title Adverse Events by Severity, Seriousness, and Relationship to Treatment
Measure 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.
Time Frame up to 12 months  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received treatment

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Adverse Events by Severity, Seriousness, and Relationship to Treatment  
[units: participants]
 
Any TEAE     58  
TEAE related to study drug     53  
TEAE with CTCAE severity grade >/=3     35  
Serious adverse event     24  
Serious adverse event related to study drug     10  
Discontinued treatment due to adverse event     11  

No statistical analysis provided for Adverse Events by Severity, Seriousness, and Relationship to Treatment



8.  Secondary:   Hematology Laboratory Abnormalities >/= Grade 3   [ Time Frame: up to 12 months ]

Measure Type Secondary
Measure Title Hematology Laboratory Abnormalities >/= Grade 3
Measure 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.
Time Frame up to 12 months  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received treatment

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Hematology Laboratory Abnormalities >/= Grade 3  
[units: participants]
 
Any >/= Grade 3 hematology laboratory abnormality     17  
Leukocytes (low)     3  
Lymphocytes (low)     10  
Neutrophils (low)     7  
Platelets (low)     3  

No statistical analysis provided for Hematology Laboratory Abnormalities >/= Grade 3



9.  Secondary:   Chemistry Laboratory Abnormalities >/= Grade 3   [ Time Frame: up to 12 months ]

Measure Type Secondary
Measure Title Chemistry Laboratory Abnormalities >/= Grade 3
Measure 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.
Time Frame up to 12 months  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received treatment

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Chemistry Laboratory Abnormalities >/= Grade 3  
[units: participants]
 
Any >/= Grade 3 chemistry laboratory abnormality     11  
Aspartate aminotransferase (high)     1  
Calcium (low)     1  
Glucose (high)     4  
Potassium (low)     1  
Sodium (low)     1  
Urate (high)     3  

No statistical analysis provided for Chemistry Laboratory Abnormalities >/= Grade 3



10.  Secondary:   Area Under the Curve   [ Time Frame: 3 weeks ]

Measure Type Secondary
Measure Title Area Under the Curve
Measure Description Area under the serum concentration-time curve from time 0 to 21 days following the first dose of brentuximab vedotin
Time Frame 3 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received treatment

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Area Under the Curve  
[units: day * microgram/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  98  
  ( 69% )  

No statistical analysis provided for Area Under the Curve



11.  Secondary:   Maximum Serum Concentration   [ Time Frame: 3 weeks ]

Measure Type Secondary
Measure Title Maximum Serum Concentration
Measure Description Maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame 3 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received treatment

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Maximum Serum Concentration  
[units: microgram/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  36  
  ( 20% )  

No statistical analysis provided for Maximum Serum Concentration



12.  Secondary:   Time of Maximum Serum Concentration   [ Time Frame: 3 weeks ]

Measure Type Secondary
Measure Title Time of Maximum Serum Concentration
Measure Description Time of maximum serum concentration from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame 3 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received treatment

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  58  
Time of Maximum Serum Concentration  
[units: days]
Median ( Full Range )
  0.02  
  ( 0.02 to 0.02 )  

No statistical analysis provided for Time of Maximum Serum Concentration



13.  Other Pre-specified:   B Symptom Resolution   [ Time Frame: up to 12 months ]

Measure Type Other Pre-specified
Measure Title B Symptom Resolution
Measure 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.
Time Frame up to 12 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants with B symptoms at baseline

Reporting Groups
  Description
Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion

Measured Values
    Brentuximab Vedotin  
Number of Participants Analyzed  
[units: participants]
  17  
B Symptom Resolution  
[units: percent of participants]
Number ( 95% Confidence Interval )
  82  
  ( 56.6 to 96.2 )  

No statistical analysis provided for B Symptom Resolution




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Maximum duration of follow-up was 17.5 months; 9 participants were continuing on treatment and 31 participants remained in survival follow-up at the time of the efficacy analyses.


  More Information