A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma

• ClinicalTrials.gov Identifier: NCT01421667
• Recruitment Status: Completed
• First Posted: August 23, 2011
• Results First Posted: October 13, 2016
• Last Update Posted: November 28, 2016
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell
• Interventions: Drug: brentuximab vedotin; Drug: rituximab
• Enrollment: 176

Participant Flow

Recruitment Details	Aug 2011 - Jun 2015
Pre-assignment Details	Four additional patients enrolled, but withdrew prior to receiving treatment.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ B-Cell NHL, BV	CD30u DLBCL, BV	CD30+ DLBCL, BV+R
Arm/Group Description	Part A - Brentuximab vedotin (BV) 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients in with CD30-positive mature T-cell non-Hodgkin lymphomas (NHL)	Part A - Brentuximab vedotin (BV) 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive B-cell non-Hodgkin lymphomas (NHL), including CD30-positive diffuse large B-cell lymphoma (DLBCL) and other CD30-positive B-cell NHLs	Part C - Brentuximab vedotin (BV) 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with diffuse large B-cell lymphoma (DLBCL) with undetectable CD30 (CD30u)	Part B - Brentuximab vedotin (BV) 1.8 mg/kg plus rituximab (R; first 8 cycles only) (375 mg/m2) every 3 weeks by intravenous (IV) infusion in patients with CD30-positive diffuse large B-cell lymphoma (DLBCL)
Period Title: Overall Study
Started	35	68	53	16
Completed	35 [1]	66 [2]	51 [3]	15 [4]
Not Completed	0	2	2	1
Reason Not Completed
Withdrawal by Subject	0	1	2	1
Lost to Follow-up	0	1	0	0
[1] Completed per protocol due to death [24] or study termination by sponsor [11]; [2] Completed per protocol due to death [45] or study termination by sponsor [21]; [3] Completed per protocol due to death [33] or study termination by sponsor [18]; [4] Completed per protocol due to death [7] or study termination by sponsor [8]

Baseline Characteristics

Arm/Group Title		CD30+ T-Cell NHL, BV	CD30+ B-Cell NHL, BV	CD30u DLBCL, BV	CD30+ DLBCL, BV+R	Total
Arm/Group Description		[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]	Total of all reporting groups
Overall Number of Baseline Participants		35	68	53	16	172
Baseline Analysis Population Description		All participants who received treatment.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
		64; (33 to 83)	57; (16 to 85)	65; (21 to 91)	62; (22 to 78)	63; (16 to 91)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
	Female	8 22.9%	29 42.6%	27 50.9%	4 25.0%	68 39.5%
	Male	27 77.1%	39 57.4%	26 49.1%	12 75.0%	104 60.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
	Hispanic or Latino	3 8.6%	3 4.4%	7 13.2%	1 6.3%	14 8.1%
	Not Hispanic or Latino	32 91.4%	65 95.6%	46 86.8%	15 93.8%	158 91.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
	American Indian or Alaska Native	0 0.0%	1 1.5%	1 1.9%	0 0.0%	2 1.2%
	Asian	1 2.9%	3 4.4%	4 7.5%	0 0.0%	8 4.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	1 1.9%	0 0.0%	1 0.6%
	Black or African American	5 14.3%	6 8.8%	4 7.5%	0 0.0%	15 8.7%
	White	29 82.9%	55 80.9%	41 77.4%	15 93.8%	140 81.4%
	More than one race	0 0.0%	3 4.4%	2 3.8%	1 6.3%	6 3.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Pathological Diagnosis; Measure Type: Number; Unit of measure: Participants	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
Diffuse Large B-Cell Lymphoma (DLBCL)		0	43	53	16	112
Epstein-Barr Virus-Associated DLBCL of Elderly		0	5	0	0	5
Follicular Lymphoma		0	3	0	0	3
Gray Zone Lymphoma		0	6	0	0	6
Primary Mediastinal B-Cell Lymphoma		0	6	0	0	6
Post-Transplant Lymphoproliferative Disorder		0	3	0	0	3
Plasmablastic Lymphoma		0	1	0	0	1
T-Cell Rich B-Cell Lymphoma		0	1	0	0	1
Angioimmunoblastic T-cell Lymphoma		13	0	0	0	13
Peripheral T-Cell Lymphoma Not Otherwise Specified		22	0	0	0	22
Transformed Disease from Prior Non-Hodgkin Lymphoma; Measure Type: Number; Unit of measure: Participants	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
Yes		1	14	11	5	31
No		34	54	42	11	141
Disease Stage; Measure Type: Number; Unit of measure: Participants	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
Stage I		2	4	1	1	8
Stage II		2	12	7	3	24
Stage III		13	17	11	6	47
Stage IV		14	31	33	6	84
Unknown		4	4	1	0	9
Bulky Disease (≥5 cm on at least one baseline index lesion); Measure Type: Number; Unit of measure: Participants	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
Yes		5	27	35	4	71
No		30	41	18	12	101
Eastern Cooperative Oncology Group Performance Status (ECOG) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
0		7	25	10	9	51
1		23	35	31	7	96
2		5	7	12	0	24
3-5		0	0	0	0	0
Missing		0	1	0	0	1
		[1] Measure Description: 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
% CD30 Expression by Visual Immunohistochemistry (vIHC) [1]; Median (Full Range); Unit of measure: Percentage
	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
		15; (0 to 95)	35; (0 to 100)	0; (0 to 10)	50; (1 to 100)	8; (0 to 100)
		[1] Measure Description: Percent CD30 expression by standard immunohistochemistry assessed visually by central laboratory (vIHC)
Refractory to Frontline Therapy; Measure Type: Number; Unit of measure: Participants	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
Yes		25	51	34	10	120
No		10	15	19	6	50
Missing/Unknown		0	2	0	0	2
Disease Status Relative to Most Recent Prior Therapy; Measure Type: Number; Unit of measure: Participants	Number Analyzed	35 participants	68 participants	53 participants	16 participants	172 participants
Refractory		22	55	37	9	123
Relapsed		13	12	16	7	48
Missing		0	1	0	0	1

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy
Description	Percentage of participants treated with brentuximab vedotin monotherapy 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 approximately 3 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment with brentuximab vedotin monotherapy and had both a baseline and at least one post-baseline disease assessment.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ Other B-Cell NHL, BV	CD30+ DLBCL, BV	CD30u DLBCL, BV
Arm/Group Description:	Part A - CD30-positive T-cell non-Hodgkin lymphomas (NHL) include pathological diagnoses of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS).	Part A - CD30-positive other B-cell non-Hodgkin lymphomas (NHL) include pathological diagnoses of follicular lymphoma, gray zone lymphoma, primary mediastinal B-cell lymphoma (PMBL), post-transplant lymphoproliferative disease (PTLD), and plasmablastic lymphoma.	Part A - CD30-positive diffuse large B-cell lymphoma (DLBCL) include pathological diagnoses of DLBCL, Epstein-Barr Virus (EBV)-associated DLBCL of the elderly, and T-cell rich B-cell lymphoma.	Part C - CD30u diffuse large B-cell lymphoma (DLBCL) includes only the pathological diagnosis of DLBCL.
Overall Number of Participants Analyzed	34	19	48	52
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	41; (24.6 to 59.3)	26; (9.1 to 51.2)	44; (29.5 to 58.8)	31; (18.7 to 45.1)

2. Primary Outcome

Title	Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab
Description	Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). 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 3 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment with brentuximab vedotin plus rituximab.

Arm/Group Title	CD30+ DLBCL, BV+R
Arm/Group Description:	Part B - CD30-positive diffuse large B-cell lymphoma (DLBCL) includes only the pathological diagnosis of DLBCL.
Overall Number of Participants Analyzed	16
Measure Type: Number; Unit of Measure: participants
Any TEAE	16
TEAE Related to Study Drug	15
TEAE With Severity Grade >/=3	9
Discontinued Treatment Due to Adverse Event	2
Serious Adverse Event	3
Serious Adverse Event Related to Study Drug	3
Deaths (Within 30 Days of Last Dose)	1
Chemistry Laboratory Abnormalities >/=Grade 3	1
Hematology Laboratory Abnormalities >/=Grade 3	7

3. Secondary Outcome

Title	Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab
Description	Percentage of participants treated with brentuximab vedotin plus rituximab 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 approximately 3 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment with brentuximab vedotin plus rituximab and had both a baseline and at least one post-baseline disease assessment.

Arm/Group Title	CD30+ DLBCL, BV+R
Arm/Group Description:	[Not Specified]
Overall Number of Participants Analyzed	12
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	50; (21.1 to 78.9)

4. Secondary Outcome

Title	Complete Remission (CR) Rate by Investigator
Description	Percentage of participants treated with brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab who achieved a best response of complete remission (CR, disappearance of all evidence of disease) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All participants who received brentuximab vedotin monotherapy or brentuximab vedotin plus rituximab and had both a baseline and at least one post-baseline disease assessment.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ Other B-Cell NHL, BV	CD30+ DLBCL, BV	CD30u DLBCL, BV	CD30+ DLBCL, BV+R
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	34	19	48	52	12
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	24; (10.7 to 41.2)	16; (3.4 to 39.6)	19; (8.9 to 32.6)	12; (4.4 to 23.4)	17; (2.1 to 48.4)

5. Secondary Outcome

Title	Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Description	Duration of complete remission (CR) or partial remission (PR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment with brentuximab vedotin monotherapy and achieved a CR or PR.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ Other B-Cell NHL, BV	CD30+ DLBCL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	14	5	21	16
Median (Full Range); Unit of Measure: months
	7.6; (1.3 to 36.1)	1.6; (1.4 to 34)	4.7; (0 to 22.7)	4.7; (0.5 to 11.6)

6. Secondary Outcome

Title	Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Description	Duration of complete remission (CR), defined as time of initial response until disease progression or death. Response criteria per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment with brentuximab vedotin monotherapy and achieved CR

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ Other B-Cell NHL, BV	CD30+ DLBCL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	8	3	9	6
Median (Full Range); Unit of Measure: months
	NA [1]; (1.8 to NA)	7.2; (1.6 to 34)	NA [1]; (2.2 to NA)	11.6; (1.4 to 11.6)

[1]

Not reached because too few events

7. Secondary Outcome

Title	Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis
Description	Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment with brentuximab vedotin monotherapy and had both a baseline and at least one post-baseline disease assessment.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ Other B-Cell NHL, BV	CD30+ DLBCL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	34	19	48	52
Median (Full Range); Unit of Measure: months
	2.5; (0.3 to 37.4)	2.9; (0.6 to 36.3)	4.0; (0.6 to 24.0)	1.4; (0.4 to 15.6)

8. Secondary Outcome

Title	Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression
Description	Percentage of participants treated with brentuximab vedotin monotherapy who achieved a best response of complete remission (CR, disappearance of all evidence of disease), partial remission (PR, regression of greater than or equal to 50% of measurable disease and no new sites), or stable disease (SD, no new sites and no change in size of previous lesions) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Patients are grouped by CD30-positivity or CD30u (undetectable CD30).
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment with brentuximab vedotin monotherapy and had both a baseline and at least one post-baseline disease assessment.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ Other B-Cell NHL, BV	CD30+ DLBCL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	34	19	48	52
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Complete Remission (CR)	24; (10.7 to 41.2)	16; (3.4 to 39.6)	19; (8.9 to 32.6)	12; (4.4 to 23.4)
Partial Remission (PR)	18; (6.8 to 34.5)	11; (1.3 to 33.1)	25; (13.6 to 39.6)	19; (9.6 to 32.5)
Disease Control Rate (CR+PR+SD)	59; (40.7 to 75.4)	63; (38.4 to 83.7)	69; (53.7 to 81.3)	42; (28.7 to 56.8)

9. Secondary Outcome

Title	Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy
Description	Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-012). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). 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 3 years

Outcome Measure Data

Analysis Population Description

All participants who received treatment with brentuximab vedotin monotherapy.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ B-Cell NHL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	35	68	53
Measure Type: Number; Unit of Measure: participants
Any TEAE	32	66	52
TEAE Related to Study Drug	28	62	39
TEAE With Severity Grade >/=3	23	52	37
Discontinued Treatment Due To Adverse Event	6	7	4
Serious Adverse Event	15	34	22
Serious Adverse Event Related to Study Drug	5	15	7
Deaths (Within 30 Days of Last Dose)	3	5	6
Chemistry Laboratory Abnormalities >/= Grade 3	8	16	10
Hematology Laboratory Abnormalities >/= Grade 3	11	31	21

10. Secondary Outcome

Title	Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1)
Description	End of infusion concentration of ADC following the first dose of brentuximab vedotin
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

All patients who were treated with brentuximab vedotin monotherapy and had Ceoi of ADC results.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ B-Cell NHL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	32	63	50
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ug/mL
	35.6; (25%)	40.0; (29%)	40.1; (43%)

11. Secondary Outcome

Title	Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1)
Description	Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

All patients who were treated with brentuximab vedotin monotherapy and had Ctrough of ADC results.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ B-Cell NHL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	25	44	34
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ug/mL
	0.44; (113%)	0.91; (119%)	0.86; (94%)

12. Secondary Outcome

Title	Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1)
Description	Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

All patients who were treated with brentuximab vedotin monotherapy and had Cmax of MMAE results.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ B-Cell NHL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	35	68	51
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	4.71; (63%)	4.66; (88%)	3.95; (74%)

13. Secondary Outcome

Title	Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Description	Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

All patients who were treated with brentuximab vedotin monotherapy and had Tmax of MMAE results.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ B-Cell NHL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	35	68	51
Median (Full Range); Unit of Measure: days
	1.90; (0.88 to 6.89)	1.91; (0.91 to 20.90)	1.94; (0.93 to 19.8)

14. Secondary Outcome

Title	Baseline Soluble CD30 Expression
Description	Serum concentration of soluble CD30 before first dose of brentuximab vedotin
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All patients who were treated with brentuximab vedotin monotherapy and had baseline sCD30 expression results.

Arm/Group Title	CD30+ T-Cell NHL, BV	CD30+ B-Cell NHL, BV	CD30u DLBCL, BV
Arm/Group Description:	[Not Specified]	[Not Specified]	[Not Specified]
Overall Number of Participants Analyzed	32	64	46
Median (Full Range); Unit of Measure: ng/mL
	1005.4; (89.4 to 26426.6)	229.4; (33.2 to 21277.7)	140.4; (53.4 to 1695.9)

Adverse Events

Time Frame	Up to 3 years
Adverse Event Reporting Description	TEAEs, defined as newly occurring (not present at baseline) or worsening after first dose of treatment
Arm/Group Title	CD30+ NHL (T-Cell and B-Cell), BV	CD30u DLBCL, BV	CD30+ DLBCL, BV+R
Arm/Group Description	Brentuximab vedotin (BV) 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients in with CD30-positive non-Hodgkin lymphomas (NHL), including T-cell lymphomas and B-cell lymphomas, as well as diffuse large B-cell lymphoma (DLBCL)	Brentuximab vedotin (BV) 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients in Part C with diffuse large B-cell lymphoma (DLBCL) with undetectable CD30 (CD30u)	Brentuximab vedotin (BV) 1.8 mg/kg plus rituximab (R; first 8 cycles only) (375 mg/m2) every 3 weeks by intravenous (IV) infusion in patients in Part B with diffuse large B-cell lymphoma (DLBCL)
All-Cause Mortality
	CD30+ NHL (T-Cell and B-Cell), BV	CD30u DLBCL, BV	CD30+ DLBCL, BV+R
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	CD30+ NHL (T-Cell and B-Cell), BV	CD30u DLBCL, BV	CD30+ DLBCL, BV+R
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	49/103 (47.57%)	22/53 (41.51%)	3/16 (18.75%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	3/103 (2.91%)	2/53 (3.77%)	1/16 (6.25%)
Neutropenia † 1	3/103 (2.91%)	0/53 (0.00%)	0/16 (0.00%)
Thrombocytopenia † 1	3/103 (2.91%)	0/53 (0.00%)	0/16 (0.00%)
Anemia † 1	1/103 (0.97%)	1/53 (1.89%)	0/16 (0.00%)
Leukopenia † 1	2/103 (1.94%)	0/53 (0.00%)	0/16 (0.00%)
Cardiac disorders
Sinus tachycardia † 1	0/103 (0.00%)	1/53 (1.89%)	1/16 (6.25%)
Cardiac arrest † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Tachycardia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Gastrointestinal disorders
Diarrhea † 1	2/103 (1.94%)	3/53 (5.66%)	0/16 (0.00%)
Nausea † 1	4/103 (3.88%)	1/53 (1.89%)	0/16 (0.00%)
Vomiting † 1	3/103 (2.91%)	1/53 (1.89%)	0/16 (0.00%)
Abdominal pain † 1	1/103 (0.97%)	1/53 (1.89%)	0/16 (0.00%)
Abdominal pain upper † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Gastric ulcer hemorrhage † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Gastritis † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Gastrointestinal hemorrhage † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Jejunal perforation † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Pancreatitis † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Small intestinal obstruction † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
General disorders
Pyrexia † 1	9/103 (8.74%)	0/53 (0.00%)	0/16 (0.00%)
Asthenia † 1	0/103 (0.00%)	2/53 (3.77%)	0/16 (0.00%)
Chest pain † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Multi-organ failure † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Pain † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Systemic inflammatory response syndrome † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Immune system disorders
Graft versus host disease † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Infections and infestations
Pneumonia † 1	8/103 (7.77%)	3/53 (5.66%)	0/16 (0.00%)
Sepsis † 1	4/103 (3.88%)	2/53 (3.77%)	0/16 (0.00%)
Urinary tract infection † 1	2/103 (1.94%)	1/53 (1.89%)	0/16 (0.00%)
Cellulitis † 1	2/103 (1.94%)	0/53 (0.00%)	0/16 (0.00%)
Breast cellulitis † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Central nervous system abscess † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Clostridium difficile colitis † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Escherichia urinary tract infection † 1	0/103 (0.00%)	0/53 (0.00%)	1/16 (6.25%)
Herpes zoster disseminated † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Infection † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Lung infection † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Mastoiditis † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Meningoencephalitis herpetic † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Peritonitis † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Pneumocystis jirovecii pneumonia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Pneumonia bacterial † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Skin infection † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Staphylococcal bacteremia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Investigations
Lipase increased † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Liver function test abnormal † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	4/103 (3.88%)	1/53 (1.89%)	0/16 (0.00%)
Hyponatremia † 1	1/103 (0.97%)	1/53 (1.89%)	1/16 (6.25%)
Decreased appetite † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Failure to thrive † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Hypercalcemia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Hyperglycemia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Hypokalemia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Hypomagnasemia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Tumor lysis syndrome † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Pain in extremity † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma † 1	6/103 (5.83%)	6/53 (11.32%)	0/16 (0.00%)
Angioimmunoblastic T-cell lymphoma † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
B-cell lymphoma † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Malignant pleural effusion † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Non-Hodgkin's lymphoma † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Peripheral T-cell lymphoma unspecified † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Nervous system disorders
Dizziness † 1	2/103 (1.94%)	0/53 (0.00%)	0/16 (0.00%)
Headache † 1	2/103 (1.94%)	0/53 (0.00%)	0/16 (0.00%)
Amnesia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Brain mass † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Encephalopathy † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Seizure † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Psychiatric disorders
Confusional state † 1	3/103 (2.91%)	0/53 (0.00%)	0/16 (0.00%)
Delirium † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Hallucination, visual † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Mental status changes † 1	0/103 (0.00%)	0/53 (0.00%)	1/16 (6.25%)
Renal and urinary disorders
Acute kidney injury † 1	5/103 (4.85%)	0/53 (0.00%)	0/16 (0.00%)
Nephrolithiasis † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Renal failure † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Renal impairment † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion † 1	2/103 (1.94%)	1/53 (1.89%)	0/16 (0.00%)
Respiratory failure † 1	2/103 (1.94%)	0/53 (0.00%)	1/16 (6.25%)
Acute respiratory distress syndrome † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Bronchostenosis † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Dyspnea † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Dyspnea exertional † 1	0/103 (0.00%)	1/53 (1.89%)	0/16 (0.00%)
Hypoxia † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Mediastinal mass † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Oropharyngeal pain † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Pneumonia aspiration † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Pulmonary alveolar hemorrhage † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Skin and subcutaneous tissue disorders
Rash † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Rash maculo-papular † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Skin lesion † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
Toxic epidermal necrolysis † 1	0/103 (0.00%)	0/53 (0.00%)	1/16 (6.25%)
Vascular disorders
Superior vena cava syndrome † 1	1/103 (0.97%)	0/53 (0.00%)	0/16 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	CD30+ NHL (T-Cell and B-Cell), BV	CD30u DLBCL, BV	CD30+ DLBCL, BV+R
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	96/103 (93.20%)	48/53 (90.57%)	15/16 (93.75%)
Blood and lymphatic system disorders
Anemia † 1	19/103 (18.45%)	8/53 (15.09%)	0/16 (0.00%)
Neutropenia † 1	31/103 (30.10%)	13/53 (24.53%)	6/16 (37.50%)
Thrombocytopenia † 1	8/103 (7.77%)	5/53 (9.43%)	1/16 (6.25%)
Cardiac disorders
Tachycardia † 1	5/103 (4.85%)	3/53 (5.66%)	1/16 (6.25%)
Gastrointestinal disorders
Abdominal distension † 1	6/103 (5.83%)	4/53 (7.55%)	1/16 (6.25%)
Abdominal pain † 1	14/103 (13.59%)	8/53 (15.09%)	2/16 (12.50%)
Constipation † 1	19/103 (18.45%)	15/53 (28.30%)	2/16 (12.50%)
Diarrhea † 1	33/103 (32.04%)	9/53 (16.98%)	4/16 (25.00%)
Nausea † 1	28/103 (27.18%)	17/53 (32.08%)	8/16 (50.00%)
Vomting † 1	19/103 (18.45%)	11/53 (20.75%)	6/16 (37.50%)
General disorders
Asthenia † 1	10/103 (9.71%)	3/53 (5.66%)	1/16 (6.25%)
Chills † 1	11/103 (10.68%)	3/53 (5.66%)	4/16 (25.00%)
Fatigue † 1	43/103 (41.75%)	17/53 (32.08%)	4/16 (25.00%)
Edema peripheral † 1	11/103 (10.68%)	4/53 (7.55%)	2/16 (12.50%)
Pyrexia † 1	22/103 (21.36%)	12/53 (22.64%)	5/16 (31.25%)
Infections and infestations
Upper respiratory tract infection † 1	10/103 (9.71%)	5/53 (9.43%)	3/16 (18.75%)
Urinary tract infection † 1	2/103 (1.94%)	7/53 (13.21%)	0/16 (0.00%)
Investigations
Weight decreased † 1	12/103 (11.65%)	6/53 (11.32%)	0/16 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	23/103 (22.33%)	9/53 (16.98%)	0/16 (0.00%)
Dehydration † 1	7/103 (6.80%)	2/53 (3.77%)	0/16 (0.00%)
Hypokalemia † 1	12/103 (11.65%)	6/53 (11.32%)	0/16 (0.00%)
Hypomagnesemia † 1	10/103 (9.71%)	2/53 (3.77%)	0/16 (0.00%)
Hyponatremia † 1	5/103 (4.85%)	4/53 (7.55%)	0/16 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	10/103 (9.71%)	1/53 (1.89%)	1/16 (6.25%)
Back pain † 1	9/103 (8.74%)	3/53 (5.66%)	0/16 (0.00%)
Pain in extremity † 1	4/103 (3.88%)	3/53 (5.66%)	3/16 (18.75%)
Nervous system disorders
Dizziness † 1	6/103 (5.83%)	5/53 (9.43%)	2/16 (12.50%)
Dysgeusia † 1	6/103 (5.83%)	3/53 (5.66%)	0/16 (0.00%)
Headache † 1	13/103 (12.62%)	6/53 (11.32%)	3/16 (18.75%)
Hypoesthesia † 1	7/103 (6.80%)	2/53 (3.77%)	1/16 (6.25%)
Peripheral motor neuropathy † 1	7/103 (6.80%)	2/53 (3.77%)	0/16 (0.00%)
Peripheral sensory neuropathy † 1	33/103 (32.04%)	14/53 (26.42%)	6/16 (37.50%)
Psychiatric disorders
Anxiety † 1	10/103 (9.71%)	3/53 (5.66%)	1/16 (6.25%)
Insomnia † 1	14/103 (13.59%)	7/53 (13.21%)	3/16 (18.75%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	17/103 (16.50%)	2/53 (3.77%)	3/16 (18.75%)
Dyspnea † 1	13/103 (12.62%)	4/53 (7.55%)	1/16 (6.25%)
Oropharyngeal pain † 1	7/103 (6.80%)	2/53 (3.77%)	1/16 (6.25%)
Skin and subcutaneous tissue disorders
Alopecia † 1	7/103 (6.80%)	3/53 (5.66%)	3/16 (18.75%)
Night sweats † 1	8/103 (7.77%)	8/53 (15.09%)	1/16 (6.25%)
Pruritus † 1	13/103 (12.62%)	5/53 (9.43%)	4/16 (25.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

[Not Specified]

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.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Seattle Genetics, Inc.
• Phone: 855-473-2436
• EMail: medinfo@seagen.com

Publications of Results:

Horwitz SM, Advani RH, Bartlett NL, Jacobsen ED, Sharman JP, O'Connor OA, Siddiqi T, Kennedy DA, Oki Y. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014 May 15;123(20):3095-100. doi: 10.1182/blood-2013-12-542142. Epub 2014 Mar 20.

Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. doi: 10.1182/blood-2014-09-598763. Epub 2015 Jan 8.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bartlett NL, Smith MR, Siddiqi T, Advani RH, O'Connor OA, Sharman JP, Feldman T, Savage KJ, Shustov AR, Diefenbach CS, Oki Y, Palanca-Wessels MC, Uttarwar M, Li M, Yang J, Jacobsen ED. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leuk Lymphoma. 2017 Jul;58(7):1607-1616. doi: 10.1080/10428194.2016.1256481. Epub 2016 Nov 20.

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT01421667
• Other Study ID Numbers: SGN35-012
• First Submitted: August 19, 2011
• First Posted: August 23, 2011
• Results First Submitted: June 21, 2016
• Results First Posted: October 13, 2016
• Last Update Posted: November 28, 2016