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: October 8, 2012

Last verified: October 2012

History of Changes

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

Hide Participant Flow

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

Hide Baseline Characteristics

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

[1]

0 = Normal activity

= Symptoms but ambulatory
= In bed <50% of the time
= In bed >50% of the time
= 100% bedridden
= Dead

[2]

Immunophenotype status with respect to anaplastic lymphoma kinase (ALK) protein

Outcome Measures

Hide All Outcome Measures

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

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Seattle Genetics, Inc.
phone: 855-473-2436
e-mail: medinfo@seagen.com

No publications provided

Responsible Party:	Seattle Genetics, Inc.
ClinicalTrials.gov Identifier:	NCT00866047 History of Changes
Other Study ID Numbers:	SG035-0004, 2008-006035-12
Study First Received:	March 19, 2009
Results First Received:	September 15, 2011
Last Updated:	October 8, 2012
Health Authority:	United States: Food and Drug Administration

To Top