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

• Sponsor: Seagen Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01421667
• Collaborator: (none)
• Enrollment: 176
• Locations: 34
• Arms: 2
• Duration (Months): 46
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label, multicenter, phase 2 clinical trial to evaluate the efficacy and safety of brentuximab vedotin as a single agent in patients with CD30-positive non-Hodgkin lymphoma (NHL) (Part A). The study will also evaluate the safety and efficacy of brentuximab vedotin in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Part B) as well as further evaluate correlation of CD30 expression and response in DLBCL (Part C).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell	Drug: brentuximab vedotin; Drug: rituximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 176 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma (NHL)
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brentuximab vedotin+rituximab	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by IV infusion; Other Names: Adcetris; SGN-35 ; Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion
Experimental: Brentuximab vedotin	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by IV infusion; Other Names: Adcetris; SGN-35

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Monotherapy [Up to approximately 3 years]

   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.

2. Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Plus Rituximab [Up to 3 years]

   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.

Secondary Outcome Measures

1. Objective Response Rate (ORR) by Investigator With Brentuximab Vedotin Plus Rituximab [Up to approximately 3 years]

   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.

2. Complete Remission (CR) Rate by Investigator [Up to approximately 3 years]

   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.

3. Duration of Objective Response With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis [Up to approximately 3 years]

   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.

4. Duration of Complete Remission With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis [Up to approximately 3 years]

   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.

5. Progression-Free Survival With Brentuximab Vedotin Monotherapy by Kaplan-Meier Analysis [Up to approximately 3 years]

   Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause

6. Correlation Between Antitumor Activity of Brentuximab Vedotin Monotherapy and CD30 Expression [Up to 3 years]

   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).

7. Adverse Events by Severity, Seriousness, and Relationship to Treatment With Brentuximab Vedotin Monotherapy [Up to 3 years]

   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.

8. Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) (Cycle 1) [1 day]

   End of infusion concentration of ADC following the first dose of brentuximab vedotin

9. Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) (Cycle 1) [3 weeks]

   Trough concentration of ADC from 0 to 21 days following the first dose of brentuximab vedotin

10. Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) (Cycle 1) [3 weeks]

    Maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin

11. Time to Maximum Concentration (Tmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) [3 weeks]

    Time of maximum serum concentration of MMAE from 0 to 21 days following the first dose of brentuximab vedotin

12. Baseline Soluble CD30 Expression [Baseline]

    Serum concentration of soluble CD30 before first dose of brentuximab vedotin

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically-confirmed NHL (DLBCL only for Parts B and C)

• Relapsed or refractory disease following at least 1 prior systemic therapy

• Measurable disease of at least 1.5 cm as documented by CT

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

Exclusion Criteria:

• History of another primary invasive malignancy that has not been in remission for at least 3 years

• Current diagnosis of systemic or cutaneous anaplastic large cell lymphoma or mycosis fungoides

• B cell lymphoma previously treated with only single-agent rituximab (for patients receiving brentuximab vedotin only) or corticosteroids as monotherapy

• Known cerebral/meningeal disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	City of Hope	Duarte	California	United States	91010-3000
3	PMK Medical Group Inc., DBA Ventura County Hematology Oncology Specialists	Oxnard	California	United States	93030
4	Stanford Cancer Center	Stanford	California	United States	94305-5821
5	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado	United States	80012
6	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
7	Cancer Specialists of North Florida - St. Augustine	St. Augustine	Florida	United States	32086
8	Emory Winship Cancer Institute	Atlanta	Georgia	United States	30322
9	Northwestern University	Chicago	Illinois	United States	60611
10	University of Chicago	Chicago	Illinois	United States	60637-1470
11	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
12	Minnesota Oncology Hematology P.A.	Minneapolis	Minnesota	United States	55404
13	Washington University School of Medicine	St. Louis	Missouri	United States	63110
14	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
15	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
16	New York Oncology Hematology, P.C.	Albany	New York	United States	12206
17	NYU Clinical Cancer Center	New York	New York	United States	10016
18	Columbia University Medical Center	New York	New York	United States	10019
19	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
20	Cleveland Clinic, The	Cleveland	Ohio	United States	44195
21	Willamette Valley Cancer and Research / USOR	Eugene	Oregon	United States	97401
22	Medical University of South Carolina	Charleston	South Carolina	United States	29425
23	St. Francis Hospital	Greenville	South Carolina	United States	29605
24	Texas Oncology - Medical City Dallas	Dallas	Texas	United States	75230
25	Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
26	Texas Oncology-Southwest Fort Worth	Fort Worth	Texas	United States	76132
27	MD Anderson Cancer Center / University of Texas	Houston	Texas	United States	77030-4003
28	Texas Oncology - Seton Williamson	Round Rock	Texas	United States	78665
29	Texas Oncology - Tyler	Tyler	Texas	United States	75702
30	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
31	Swedish Cancer Institute Medical Oncology	Edmonds	Washington	United States	98026
32	Seattle Cancer Care Alliance / University of Washington Medical Center	Seattle	Washington	United States	98109
33	Northwest Cancer Specialists, P.C.	Vancouver	Washington	United States	98684
34	British Columbia Cancer Agency - Vancouver Centre	Vancouver	British Columbia	Canada	V5Z 4E6

Sponsors and Collaborators

• Seagen Inc.

Investigators

• Study Director: Corinna Palanca-Wessels, MD, PhD, Seagen Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT01421667
• Other Study ID Numbers: SGN35-012
• First Posted: Aug 23, 2011
• Last Update Posted: Nov 28, 2016
• Last Verified: Jun 1, 2015

• Keywords provided by Seagen Inc.: Lymphoma, Large B-Cell, Diffuse; Antigens, CD30; Antibody-Drug Conjugate; Antibodies, Monoclonal; Lymphoma, Non-Hodgkin; Monomethyl auristatin E; Drug Therapy; Immunotherapy; Hematologic Diseases; Lymphoma; Lymphoma, B-Cell; Lymphoma, T-Cell
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Rituximab; Brentuximab Vedotin

Study Results

Participant Flow

Recruitment Details	Aug 2011 - Jun 2015
Pre-assignment Detail	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	66	51	15
NOT COMPLETED	0	2	2	1

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	Total of all reporting groups
Overall Participants	35	68	53	16	172
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	57	65	62	63
Sex: Female, Male (Count of Participants)
Female	8 22.9%	29 42.6%	27 50.9%	4 25%	68 39.5%
Male	27 77.1%	39 57.4%	26 49.1%	12 75%	104 60.5%
Ethnicity (NIH/OMB) (Count of 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%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.5%	1 1.9%	0 0%	2 1.2%
Asian	1 2.9%	3 4.4%	4 7.5%	0 0%	8 4.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 1.9%	0 0%	1 0.6%
Black or African American	5 14.3%	6 8.8%	4 7.5%	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%	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%
Pathological Diagnosis (participants) [Number]
Diffuse Large B-Cell Lymphoma (DLBCL)	0 0%	43 63.2%	53 100%	16 100%	112 65.1%
Epstein-Barr Virus-Associated DLBCL of Elderly	0 0%	5 7.4%	0 0%	0 0%	5 2.9%
Follicular Lymphoma	0 0%	3 4.4%	0 0%	0 0%	3 1.7%
Gray Zone Lymphoma	0 0%	6 8.8%	0 0%	0 0%	6 3.5%
Primary Mediastinal B-Cell Lymphoma	0 0%	6 8.8%	0 0%	0 0%	6 3.5%
Post-Transplant Lymphoproliferative Disorder	0 0%	3 4.4%	0 0%	0 0%	3 1.7%
Plasmablastic Lymphoma	0 0%	1 1.5%	0 0%	0 0%	1 0.6%
T-Cell Rich B-Cell Lymphoma	0 0%	1 1.5%	0 0%	0 0%	1 0.6%
Angioimmunoblastic T-cell Lymphoma	13 37.1%	0 0%	0 0%	0 0%	13 7.6%
Peripheral T-Cell Lymphoma Not Otherwise Specified	22 62.9%	0 0%	0 0%	0 0%	22 12.8%
Transformed Disease from Prior Non-Hodgkin Lymphoma (participants) [Number]
Yes	1 2.9%	14 20.6%	11 20.8%	5 31.3%	31 18%
No	34 97.1%	54 79.4%	42 79.2%	11 68.8%	141 82%
Disease Stage (participants) [Number]
Stage I	2 5.7%	4 5.9%	1 1.9%	1 6.3%	8 4.7%
Stage II	2 5.7%	12 17.6%	7 13.2%	3 18.8%	24 14%
Stage III	13 37.1%	17 25%	11 20.8%	6 37.5%	47 27.3%
Stage IV	14 40%	31 45.6%	33 62.3%	6 37.5%	84 48.8%
Unknown	4 11.4%	4 5.9%	1 1.9%	0 0%	9 5.2%
Bulky Disease (≥5 cm on at least one baseline index lesion) (participants) [Number]
Yes	5 14.3%	27 39.7%	35 66%	4 25%	71 41.3%
No	30 85.7%	41 60.3%	18 34%	12 75%	101 58.7%
Eastern Cooperative Oncology Group Performance Status (ECOG) (participants) [Number]
0	7 20%	25 36.8%	10 18.9%	9 56.3%	51 29.7%
1	23 65.7%	35 51.5%	31 58.5%	7 43.8%	96 55.8%
2	5 14.3%	7 10.3%	12 22.6%	0 0%	24 14%
3-5	0 0%	0 0%	0 0%	0 0%	0 0%
Missing	0 0%	1 1.5%	0 0%	0 0%	1 0.6%
% CD30 Expression by Visual Immunohistochemistry (vIHC) (percentage) [Median (Full Range) ]
Median (Full Range) [percentage]	15	35	0	50	8
Refractory to Frontline Therapy (participants) [Number]
Yes	25 71.4%	51 75%	34 64.2%	10 62.5%	120 69.8%
No	10 28.6%	15 22.1%	19 35.8%	6 37.5%	50 29.1%
Missing/Unknown	0 0%	2 2.9%	0 0%	0 0%	2 1.2%
Disease Status Relative to Most Recent Prior Therapy (participants) [Number]
Refractory	22 62.9%	55 80.9%	37 69.8%	9 56.3%	123 71.5%
Relapsed	13 37.1%	12 17.6%	16 30.2%	7 43.8%	48 27.9%
Missing	0 0%	1 1.5%	0 0%	0 0%	1 0.6%

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.
Measure Participants	34	19	48	52
Number (95% Confidence Interval) [percentage of participants]	41 117.1%	26 38.2%	44 83%	31 193.8%

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.
Measure Participants	16
Any TEAE	16 45.7%
TEAE Related to Study Drug	15 42.9%
TEAE With Severity Grade >/=3	9 25.7%
Discontinued Treatment Due to Adverse Event	2 5.7%
Serious Adverse Event	3 8.6%
Serious Adverse Event Related to Study Drug	3 8.6%
Deaths (Within 30 Days of Last Dose)	1 2.9%
Chemistry Laboratory Abnormalities >/=Grade 3	1 2.9%
Hematology Laboratory Abnormalities >/=Grade 3	7 20%

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
Measure Participants	12
Number (95% Confidence Interval) [percentage of participants]	50 142.9%

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
Measure Participants	34	19	48	52	12
Number (95% Confidence Interval) [percentage of participants]	24 68.6%	16 23.5%	19 35.8%	12 75%	17 9.9%

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
Measure Participants	14	5	21	16
Median (Full Range) [months]	7.6	1.6	4.7	4.7

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
Measure Participants	8	3	9	6
Median (Full Range) [months]	NA	7.2	NA	11.6

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
Measure Participants	34	19	48	52
Median (Full Range) [months]	2.5	2.9	4.0	1.4

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
Measure Participants	34	19	48	52
Complete Remission (CR)	24 68.6%	16 23.5%	19 35.8%	12 75%
Partial Remission (PR)	18 51.4%	11 16.2%	25 47.2%	19 118.8%
Disease Control Rate (CR+PR+SD)	59 168.6%	63 92.6%	69 130.2%	42 262.5%

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
Measure Participants	35	68	53
Any TEAE	32 91.4%	66 97.1%	52 98.1%
TEAE Related to Study Drug	28 80%	62 91.2%	39 73.6%
TEAE With Severity Grade >/=3	23 65.7%	52 76.5%	37 69.8%
Discontinued Treatment Due To Adverse Event	6 17.1%	7 10.3%	4 7.5%
Serious Adverse Event	15 42.9%	34 50%	22 41.5%
Serious Adverse Event Related to Study Drug	5 14.3%	15 22.1%	7 13.2%
Deaths (Within 30 Days of Last Dose)	3 8.6%	5 7.4%	6 11.3%
Chemistry Laboratory Abnormalities >/= Grade 3	8 22.9%	16 23.5%	10 18.9%
Hematology Laboratory Abnormalities >/= Grade 3	11 31.4%	31 45.6%	21 39.6%

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
Measure Participants	32	63	50
Geometric Mean (Geometric Coefficient of Variation) [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
Measure Participants	25	44	34
Geometric Mean (Geometric Coefficient of Variation) [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
Measure Participants	35	68	51
Geometric Mean (Geometric Coefficient of Variation) [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
Measure Participants	35	68	51
Median (Full Range) [days]	1.90	1.91	1.94

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
Measure Participants	32	64	46
Median (Full Range) [ng/mL]	1005.4	229.4	140.4

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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	CD30+ NHL (T-Cell and B-Cell), BV		CD30u DLBCL, BV		CD30+ DLBCL, BV+R
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/103 (47.6%)		22/53 (41.5%)		3/16 (18.8%)
Blood and lymphatic system disorders
Febrile neutropenia	3/103 (2.9%)		2/53 (3.8%)		1/16 (6.3%)
Neutropenia	3/103 (2.9%)		0/53 (0%)		0/16 (0%)
Thrombocytopenia	3/103 (2.9%)		0/53 (0%)		0/16 (0%)
Anemia	1/103 (1%)		1/53 (1.9%)		0/16 (0%)
Leukopenia	2/103 (1.9%)		0/53 (0%)		0/16 (0%)
Cardiac disorders
Sinus tachycardia	0/103 (0%)		1/53 (1.9%)		1/16 (6.3%)
Cardiac arrest	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Tachycardia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Ear and labyrinth disorders
Vertigo	1/103 (1%)		0/53 (0%)		0/16 (0%)
Gastrointestinal disorders
Diarrhea	2/103 (1.9%)		3/53 (5.7%)		0/16 (0%)
Nausea	4/103 (3.9%)		1/53 (1.9%)		0/16 (0%)
Vomiting	3/103 (2.9%)		1/53 (1.9%)		0/16 (0%)
Abdominal pain	1/103 (1%)		1/53 (1.9%)		0/16 (0%)
Abdominal pain upper	1/103 (1%)		0/53 (0%)		0/16 (0%)
Gastric ulcer hemorrhage	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Gastritis	1/103 (1%)		0/53 (0%)		0/16 (0%)
Gastrointestinal hemorrhage	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Jejunal perforation	1/103 (1%)		0/53 (0%)		0/16 (0%)
Pancreatitis	1/103 (1%)		0/53 (0%)		0/16 (0%)
Small intestinal obstruction	1/103 (1%)		0/53 (0%)		0/16 (0%)
General disorders
Pyrexia	9/103 (8.7%)		0/53 (0%)		0/16 (0%)
Asthenia	0/103 (0%)		2/53 (3.8%)		0/16 (0%)
Chest pain	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Multi-organ failure	1/103 (1%)		0/53 (0%)		0/16 (0%)
Pain	1/103 (1%)		0/53 (0%)		0/16 (0%)
Systemic inflammatory response syndrome	1/103 (1%)		0/53 (0%)		0/16 (0%)
Immune system disorders
Graft versus host disease	1/103 (1%)		0/53 (0%)		0/16 (0%)
Infections and infestations
Pneumonia	8/103 (7.8%)		3/53 (5.7%)		0/16 (0%)
Sepsis	4/103 (3.9%)		2/53 (3.8%)		0/16 (0%)
Urinary tract infection	2/103 (1.9%)		1/53 (1.9%)		0/16 (0%)
Cellulitis	2/103 (1.9%)		0/53 (0%)		0/16 (0%)
Breast cellulitis	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Central nervous system abscess	1/103 (1%)		0/53 (0%)		0/16 (0%)
Clostridium difficile colitis	1/103 (1%)		0/53 (0%)		0/16 (0%)
Escherichia urinary tract infection	0/103 (0%)		0/53 (0%)		1/16 (6.3%)
Herpes zoster disseminated	1/103 (1%)		0/53 (0%)		0/16 (0%)
Infection	1/103 (1%)		0/53 (0%)		0/16 (0%)
Lung infection	1/103 (1%)		0/53 (0%)		0/16 (0%)
Mastoiditis	1/103 (1%)		0/53 (0%)		0/16 (0%)
Meningoencephalitis herpetic	1/103 (1%)		0/53 (0%)		0/16 (0%)
Peritonitis	1/103 (1%)		0/53 (0%)		0/16 (0%)
Pneumocystis jirovecii pneumonia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Pneumonia bacterial	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Skin infection	1/103 (1%)		0/53 (0%)		0/16 (0%)
Staphylococcal bacteremia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Investigations
Lipase increased	1/103 (1%)		0/53 (0%)		0/16 (0%)
Liver function test abnormal	1/103 (1%)		0/53 (0%)		0/16 (0%)
Metabolism and nutrition disorders
Dehydration	4/103 (3.9%)		1/53 (1.9%)		0/16 (0%)
Hyponatremia	1/103 (1%)		1/53 (1.9%)		1/16 (6.3%)
Decreased appetite	1/103 (1%)		0/53 (0%)		0/16 (0%)
Failure to thrive	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Hypercalcemia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Hyperglycemia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Hypokalemia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Hypomagnasemia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Tumor lysis syndrome	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/103 (1%)		0/53 (0%)		0/16 (0%)
Pain in extremity	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma	6/103 (5.8%)		6/53 (11.3%)		0/16 (0%)
Angioimmunoblastic T-cell lymphoma	1/103 (1%)		0/53 (0%)		0/16 (0%)
B-cell lymphoma	1/103 (1%)		0/53 (0%)		0/16 (0%)
Malignant pleural effusion	1/103 (1%)		0/53 (0%)		0/16 (0%)
Non-Hodgkin's lymphoma	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Peripheral T-cell lymphoma unspecified	1/103 (1%)		0/53 (0%)		0/16 (0%)
Nervous system disorders
Dizziness	2/103 (1.9%)		0/53 (0%)		0/16 (0%)
Headache	2/103 (1.9%)		0/53 (0%)		0/16 (0%)
Amnesia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Brain mass	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Encephalopathy	1/103 (1%)		0/53 (0%)		0/16 (0%)
Seizure	1/103 (1%)		0/53 (0%)		0/16 (0%)
Psychiatric disorders
Confusional state	3/103 (2.9%)		0/53 (0%)		0/16 (0%)
Delirium	1/103 (1%)		0/53 (0%)		0/16 (0%)
Hallucination, visual	1/103 (1%)		0/53 (0%)		0/16 (0%)
Mental status changes	0/103 (0%)		0/53 (0%)		1/16 (6.3%)
Renal and urinary disorders
Acute kidney injury	5/103 (4.9%)		0/53 (0%)		0/16 (0%)
Nephrolithiasis	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Renal failure	1/103 (1%)		0/53 (0%)		0/16 (0%)
Renal impairment	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/103 (1.9%)		1/53 (1.9%)		0/16 (0%)
Respiratory failure	2/103 (1.9%)		0/53 (0%)		1/16 (6.3%)
Acute respiratory distress syndrome	1/103 (1%)		0/53 (0%)		0/16 (0%)
Bronchostenosis	1/103 (1%)		0/53 (0%)		0/16 (0%)
Dyspnea	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Dyspnea exertional	0/103 (0%)		1/53 (1.9%)		0/16 (0%)
Hypoxia	1/103 (1%)		0/53 (0%)		0/16 (0%)
Mediastinal mass	1/103 (1%)		0/53 (0%)		0/16 (0%)
Oropharyngeal pain	1/103 (1%)		0/53 (0%)		0/16 (0%)
Pneumonia aspiration	1/103 (1%)		0/53 (0%)		0/16 (0%)
Pulmonary alveolar hemorrhage	1/103 (1%)		0/53 (0%)		0/16 (0%)
Skin and subcutaneous tissue disorders
Rash	1/103 (1%)		0/53 (0%)		0/16 (0%)
Rash maculo-papular	1/103 (1%)		0/53 (0%)		0/16 (0%)
Skin lesion	1/103 (1%)		0/53 (0%)		0/16 (0%)
Toxic epidermal necrolysis	0/103 (0%)		0/53 (0%)		1/16 (6.3%)
Vascular disorders
Superior vena cava syndrome	1/103 (1%)		0/53 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	CD30+ NHL (T-Cell and B-Cell), BV		CD30u DLBCL, BV		CD30+ DLBCL, BV+R
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/103 (93.2%)		48/53 (90.6%)		15/16 (93.8%)
Blood and lymphatic system disorders
Anemia	19/103 (18.4%)		8/53 (15.1%)		0/16 (0%)
Neutropenia	31/103 (30.1%)		13/53 (24.5%)		6/16 (37.5%)
Thrombocytopenia	8/103 (7.8%)		5/53 (9.4%)		1/16 (6.3%)
Cardiac disorders
Tachycardia	5/103 (4.9%)		3/53 (5.7%)		1/16 (6.3%)
Gastrointestinal disorders
Abdominal distension	6/103 (5.8%)		4/53 (7.5%)		1/16 (6.3%)
Abdominal pain	14/103 (13.6%)		8/53 (15.1%)		2/16 (12.5%)
Constipation	19/103 (18.4%)		15/53 (28.3%)		2/16 (12.5%)
Diarrhea	33/103 (32%)		9/53 (17%)		4/16 (25%)
Nausea	28/103 (27.2%)		17/53 (32.1%)		8/16 (50%)
Vomting	19/103 (18.4%)		11/53 (20.8%)		6/16 (37.5%)
General disorders
Asthenia	10/103 (9.7%)		3/53 (5.7%)		1/16 (6.3%)
Chills	11/103 (10.7%)		3/53 (5.7%)		4/16 (25%)
Fatigue	43/103 (41.7%)		17/53 (32.1%)		4/16 (25%)
Edema peripheral	11/103 (10.7%)		4/53 (7.5%)		2/16 (12.5%)
Pyrexia	22/103 (21.4%)		12/53 (22.6%)		5/16 (31.3%)
Infections and infestations
Upper respiratory tract infection	10/103 (9.7%)		5/53 (9.4%)		3/16 (18.8%)
Urinary tract infection	2/103 (1.9%)		7/53 (13.2%)		0/16 (0%)
Investigations
Weight decreased	12/103 (11.7%)		6/53 (11.3%)		0/16 (0%)
Metabolism and nutrition disorders
Decreased appetite	23/103 (22.3%)		9/53 (17%)		0/16 (0%)
Dehydration	7/103 (6.8%)		2/53 (3.8%)		0/16 (0%)
Hypokalemia	12/103 (11.7%)		6/53 (11.3%)		0/16 (0%)
Hypomagnesemia	10/103 (9.7%)		2/53 (3.8%)		0/16 (0%)
Hyponatremia	5/103 (4.9%)		4/53 (7.5%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/103 (9.7%)		1/53 (1.9%)		1/16 (6.3%)
Back pain	9/103 (8.7%)		3/53 (5.7%)		0/16 (0%)
Pain in extremity	4/103 (3.9%)		3/53 (5.7%)		3/16 (18.8%)
Nervous system disorders
Dizziness	6/103 (5.8%)		5/53 (9.4%)		2/16 (12.5%)
Dysgeusia	6/103 (5.8%)		3/53 (5.7%)		0/16 (0%)
Headache	13/103 (12.6%)		6/53 (11.3%)		3/16 (18.8%)
Hypoesthesia	7/103 (6.8%)		2/53 (3.8%)		1/16 (6.3%)
Peripheral motor neuropathy	7/103 (6.8%)		2/53 (3.8%)		0/16 (0%)
Peripheral sensory neuropathy	33/103 (32%)		14/53 (26.4%)		6/16 (37.5%)
Psychiatric disorders
Anxiety	10/103 (9.7%)		3/53 (5.7%)		1/16 (6.3%)
Insomnia	14/103 (13.6%)		7/53 (13.2%)		3/16 (18.8%)
Respiratory, thoracic and mediastinal disorders
Cough	17/103 (16.5%)		2/53 (3.8%)		3/16 (18.8%)
Dyspnea	13/103 (12.6%)		4/53 (7.5%)		1/16 (6.3%)
Oropharyngeal pain	7/103 (6.8%)		2/53 (3.8%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Alopecia	7/103 (6.8%)		3/53 (5.7%)		3/16 (18.8%)
Night sweats	8/103 (7.8%)		8/53 (15.1%)		1/16 (6.3%)
Pruritus	13/103 (12.6%)		5/53 (9.4%)		4/16 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.