Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies

• Sponsor: Seagen Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01461538
• Collaborator: (none)
• Enrollment: 84
• Locations: 29
• Arms: 3
• Duration (Months): 38
• Patients Per Site: 2.9
• 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 antitumor activity of brentuximab vedotin as a single agent in patients with CD30-positive nonlymphomatous malignancies.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoid Leukemia; Acute Myeloid Leukemia; Anemia, Refractory, With Excess of Blasts; Solid Tumors	Drug: brentuximab vedotin; Drug: brentuximab vedotin; Drug: brentuximab vedotin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label Study of Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brentuximab vedotin 1.8 mg/kg Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35
Experimental: Brentuximab vedotin 2.4 mg/kg Brentuximab vedotin 2.4 mg/kg every 3 weeks by IV infusion	Drug: brentuximab vedotin; 2.4 mg/kg every 3 weeks by intravenous (IV) infusion; Other Names: Adcetris; SGN-35
Experimental: Brentuximab vedotin 1.2 mg/kg Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by IV infusion	Drug: brentuximab vedotin; 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion; Other Names: Adcetris; SGN-35

Outcome Measures

Primary Outcome Measures

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

   Percentage of participants who achieved a best response of complete response/remission (CR), CR without hematologic recovery (CRi; leukemia only), or partial remission (PR) per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).

Secondary Outcome Measures

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

   Percentage of participants who achieved a best response of CR per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).

2. Duration of Objective Response by Kaplan-Meier Analysis [Up to approximately 2 years]

   Duration of objective response (CR [+CRi; leukemia] + PR), defined as time of initial response until disease progression or death. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).

3. Duration of Complete Response by Kaplan-Meier Analysis [Up to approximately 2 years]

   Duration of CR, defined as time of initial response until disease progression or death. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).

4. Progression-Free Survival by Kaplan-Meier Analysis [Up to approximately 2 years]

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

5. Adverse Events by Severity, Seriousness, and Relationship to Treatment [Up to approximately 3 years]

   Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-013). 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.

6. Laboratory Abnormalities >/= Grade 3 [Up to approximately 3 years]

   Counts of study participants with post-baseline laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 4.03. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category

7. Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) [Up to approximately 3 years]

8. Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) [Up to approximately 3 years]

9. Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) [Up to approximately 3 years]

10. Brentuximab Vedotin Monomethyl Auristatin E (MMAE) Trough Concentration (Ctrough) [Up to approximately 3 years]

11. Incidence of Anti-therapeutic Antibodies (ATA) [Up to approximately 3 years]

    Counts of participants with post-baseline anti-brentuximab vedotin antibodies. Persistently positive is defined as confirmed ATA in more than 2 post-baseline samples and transiently positive is defined as confirmed ATA in 1 or 2 post-baseline samples.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically-confirmed by central review CD30-positive nonlymphomatous malignancy

• Have failed, refused, or have been deemed ineligible for standard therapy

• Measurable disease

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 or a Karnofsky or Lansky Performance Status score greater than or equal to 70

Exclusion Criteria:

• Primary diagnosis of lymphoma or central nervous system (CNS) malignancy

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

• Evidence of active 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	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado	United States	80012
5	Mayo Clinic Cancer Center	Jacksonville	Florida	United States	32224
6	Ocala Oncology Center	Ocala	Florida	United States	34471
7	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
8	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
9	Minnesota Oncology Hematology P.A.	Minneapolis	Minnesota	United States	55404
10	New York Oncology Hematology, P.C.	Albany	New York	United States	12206
11	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106-5055
12	Willamette Valley Cancer and Research / USOR	Eugene	Oregon	United States	97401
13	Northwest Cancer Specialists, P.C.	Tulatin	Oregon	United States	97062
14	St. Francis Hospital	Greenville	South Carolina	United States	29605
15	Texas Oncology - Bedford	Bedford	Texas	United States	76022
16	Texas Oncology - Medical City Dallas	Dallas	Texas	United States	75230
17	Texas Oncology - Dallas Presbyterian	Dallas	Texas	United States	75231
18	Texas Oncology Denton South	Denton	Texas	United States	76210
19	Texas Oncology - Fort Worth 12th Avenue	Fort Worth	Texas	United States	76104
20	MD Anderson Cancer Center / University of Texas	Houston	Texas	United States	77030-4003
21	MD Anderson Cancer Center Leukemia Group	Houston	Texas	United States	77030
22	Texas Oncology - Central Austin Cancer Center	Round Rock	Texas	United States	78731
23	Cancer Centers of South Texas - HOAST	San Antonio	Texas	United States	78229
24	Texas Oncology - Waco	Waco	Texas	United States	76712
25	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Blacksburg	Virginia	United States	24060
26	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
27	Puget Sound Cancer Centers	Edmonds	Washington	United States	98026
28	Cancer Care Northwest	Spokane Valley	Washington	United States	99216
29	Yakima Valley Memorial Hospital / North Star Lodge	Yakima	Washington	United States	98902

Sponsors and Collaborators

• Seagen Inc.

Investigators

• Study Director: Neil Josephson, MD, Seagen Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT01461538
• Other Study ID Numbers: SGN35-013
• First Posted: Oct 28, 2011
• Last Update Posted: Mar 4, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Seagen Inc.: Acute Lymphoid Leukemia; Myelodysplastic Syndrome; Acute Myeloid Leukemia; Solid Tumors; Anemia, Refractory, with Excess of Blasts; Antibodies, Monoclonal; Antibody-Drug Conjugate; Antigens, CD30; Drug Therapy; Hematologic Diseases; Immunotherapy; Monomethyl Auristatin E
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Brentuximab Vedotin; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	Oct 2011 - Dec 2014
Pre-assignment Detail	One additional patient enrolled, but withdrew prior to treatment group assignment.

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
Period Title: Overall Study
STARTED	46	28	9
COMPLETED	28	20	7
NOT COMPLETED	18	8	2

Baseline Characteristics

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week	Total
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)	Total of all reporting groups
Overall Participants	46	28	9	83
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	64	76	65
Sex: Female, Male (Count of Participants)
Female	21 45.7%	12 42.9%	4 44.4%	37 44.6%
Male	25 54.3%	16 57.1%	5 55.6%	46 55.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.3%	2 7.1%	0 0%	4 4.8%
Not Hispanic or Latino	44 95.7%	26 92.9%	9 100%	79 95.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 2.2%	2 7.1%	0 0%	3 3.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 4.3%	0 0%	0 0%	2 2.4%
White	42 91.3%	25 89.3%	9 100%	76 91.6%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.2%	1 3.6%	0 0%	2 2.4%
Region of Enrollment (participants) [Number]
United States	46 100%	28 100%	9 100%	83 100%
Eastern Cooperative Oncology Group Performance Status (participants) [Number]
0	13 28.3%	5 17.9%	1 11.1%	19 22.9%
1	20 43.5%	15 53.6%	5 55.6%	40 48.2%
2	0 0%	0 0%	1 11.1%	1 1.2%
3-5	0 0%	0 0%	0 0%	0 0%
Missing	13 28.3%	8 28.6%	2 22.2%	23 27.7%
Height (centimeters (cm)) [Median (Full Range) ]
Median (Full Range) [centimeters (cm)]	170.2	171.9	167.6	170.2
Weight (kilograms (kg)) [Median (Full Range) ]
Median (Full Range) [kilograms (kg)]	74.8	75.1	73.4	74.8
Body Mass Index (kg per meter squared (kg/m^2)) [Median (Full Range) ]
Median (Full Range) [kg per meter squared (kg/m^2)]	25.3	27.4	26.3	26.0

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) by Investigator
Description	Percentage of participants who achieved a best response of complete response/remission (CR), CR without hematologic recovery (CRi; leukemia only), or partial remission (PR) per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

Efficacy-evaluable population

Arm/Group Title	Solid Tumors	Leukemia
Arm/Group Description	Participants with solid tumors	Participants with acute leukemia or high grade MDS (refractory anemia with excess blasts-2)
Measure Participants	59	14
Number (95% Confidence Interval) [percentage of participants]	12 26.1%	14 50%

2. Secondary Outcome

Title	Complete Remission (CR) Rate by Investigator
Description	Percentage of participants who achieved a best response of CR per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

Efficacy-evaluable population

Arm/Group Title	Solid Tumors	Leukemia
Arm/Group Description	Participants with solid tumors	Participants with acute leukemia or high grade MDS (refractory anemia with excess blasts-2)
Measure Participants	59	14
Number (95% Confidence Interval) [percentage of participants]	2 4.3%	0 0%

3. Secondary Outcome

Title	Duration of Objective Response by Kaplan-Meier Analysis
Description	Duration of objective response (CR [+CRi; leukemia] + PR), defined as time of initial response until disease progression or death. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

Participants with objective response (CR [+CRi; leukemia] + PR)

Arm/Group Title	Solid Tumors	Leukemia
Arm/Group Description	Participants with solid tumors	Participants with acute leukemia or high grade MDS (refractory anemia with excess blasts-2)
Measure Participants	7	2
Median (Full Range) [months]	2.9	2.1

4. Secondary Outcome

Title	Duration of Complete Response by Kaplan-Meier Analysis
Description	Duration of CR, defined as time of initial response until disease progression or death. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003).
Time Frame	Up to approximately 2 years

Outcome Measure Data

Analysis Population Description

Participants with CR

Arm/Group Title	Solid Tumors	Leukemia
Arm/Group Description	Participants with solid tumors	Participants with acute leukemia or high grade MDS (refractory anemia with excess blasts-2)
Measure Participants	1	0
Median (Full Range) [months]	22.3

5. Secondary Outcome

Title	Progression-Free Survival 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 2 years

Outcome Measure Data

Analysis Population Description

All treated patients, excluding 3 patients without available response results

Arm/Group Title	Solid Tumors	Leukemia
Arm/Group Description	Participants with solid tumors	Participants with acute leukemia or high grade MDS (refractory anemia with excess blasts-2)
Measure Participants	63	17
Median (95% Confidence Interval) [months]	2.1	0.7

6. Secondary Outcome

Title	Adverse Events by Severity, Seriousness, and Relationship to Treatment
Description	Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-013). 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 approximately 3 years

Outcome Measure Data

Analysis Population Description

All treated patients

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
Measure Participants	46	28	9
Any TEAE	45 97.8%	28 100%	9 100%
TEAE related to study drug	31 67.4%	24 85.7%	5 55.6%
TEAE with severity grade >/=3	31 67.4%	18 64.3%	7 77.8%
Discontinued treatment due to adverse event	5 10.9%	2 7.1%	2 22.2%
Serious adverse event	24 52.2%	13 46.4%	5 55.6%
Serious adverse event related to study drug	5 10.9%	6 21.4%	2 22.2%
Deaths (within 30 days of last dose)	10 21.7%	6 21.4%	2 22.2%

7. Secondary Outcome

Title	Laboratory Abnormalities >/= Grade 3
Description	Counts of study participants with post-baseline laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 4.03. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All treated patients

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
Measure Participants	46	28	9
Any >/= Grade 3 laboratory abnormality	24 52.2%	12 42.9%	9 100%
Alanine aminotransferase high	0 0%	1 3.6%	1 11.1%
Albumin low	2 4.3%	3 10.7%	0 0%
Alkaline phosphatase high	0 0%	1 3.6%	0 0%
Aspartate aminotransferase high	0 0%	1 3.6%	0 0%
Bilirubin high	0 0%	1 3.6%	0 0%
Calcium low	1 2.2%	1 3.6%	0 0%
Glucose high	2 4.3%	1 3.6%	0 0%
Glucose low	1 2.2%	0 0%	0 0%
Sodium low	4 8.7%	2 7.1%	0 0%
Urate high	2 4.3%	0 0%	0 0%
Prothrombin INR high	0 0%	0 0%	1 11.1%
Absolute neutrophil count low	6 13%	2 7.1%	5 55.6%
Hemoglobin low	4 8.7%	0 0%	3 33.3%
Leukocytes high	0 0%	1 3.6%	1 11.1%
Leukocytes low	4 8.7%	0 0%	4 44.4%
Lymphocytes high	1 2.2%	2 7.1%	0 0%
Lymphocytes low	9 19.6%	3 10.7%	1 11.1%
Neutrophils low	6 13%	3 10.7%	7 77.8%
Platelets low	4 8.7%	4 14.3%	7 77.8%

8. Secondary Outcome

Title	Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi)
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All treated patients with available ADC Ceoi results

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
Measure Participants	42	25	9
Geometric Mean (Geometric Coefficient of Variation) [ug/mL]	40 (26)	54 (28)	25 (23)

9. Secondary Outcome

Title	Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough)
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All treated patients with available ADC Ctrough results

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
Measure Participants	34	10	9
Geometric Mean (Geometric Coefficient of Variation) [ug/mL]	0.36 (180)	0.55 (210)	1.5 (48)

10. Secondary Outcome

Title	Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All treated patients with available Cmax of MMAE results

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
Measure Participants	43	25	9
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	4.0 (78)	6.2 (71)	2.6 (83)

11. Secondary Outcome

Title	Brentuximab Vedotin Monomethyl Auristatin E (MMAE) Trough Concentration (Ctrough)
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

All treated patients with available MMAE Ctrough results

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
Measure Participants	34	11	9
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	0.22 (92)	0.35 (82)	1.5 (65)

12. Secondary Outcome

Title	Incidence of Anti-therapeutic Antibodies (ATA)
Description	Counts of participants with post-baseline anti-brentuximab vedotin antibodies. Persistently positive is defined as confirmed ATA in more than 2 post-baseline samples and transiently positive is defined as confirmed ATA in 1 or 2 post-baseline samples.
Time Frame	Up to approximately 3 years

Outcome Measure Data

Analysis Population Description

Immunogenicity-evaluable set

Arm/Group Title	BV 1.8 mg/kg Q3Week	BV 2.4 mg/kg Q3Week	BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia	Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
Measure Participants	36	23	8
Baseline (BL) negative	33 71.7%	21 75%	8 88.9%
BL negative, negative post-BL	14 30.4%	14 50%	8 88.9%
BL negative, transiently positive post-BL	18 39.1%	6 21.4%	0 0%
BL negative, persistently positive post-BL	1 2.2%	1 3.6%	0 0%
BL positive	3 6.5%	2 7.1%	0 0%
BL positive, negative post-BL	1 2.2%	0 0%	0 0%
BL positive, transiently positive post-BL	2 4.3%	1 3.6%	0 0%
BL positive, persistently positive post-BL	0 0%	1 3.6%	0 0%

Adverse Events

Time Frame	Up to approximately 3 years
Adverse Event Reporting Description	TEAEs, defined as newly occurring (not present at baseline) or worsening after first dose of brentuximab vedotin
Arm/Group Title	BV 1.8 mg/kg Q3Week		BV 2.4 mg/kg Q3Week		BV 1.2 mg/kg Q1Week
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia		Brentuximab vedotin 2.4 mg/kg every 3 weeks by intravenous (IV) infusion in patients with CD30-positive solid tumors or leukemia		Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion in patients with acute leukemia or myelodysplastic syndrome (MDS)
All Cause Mortality
	BV 1.8 mg/kg Q3Week		BV 2.4 mg/kg Q3Week		BV 1.2 mg/kg Q1Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	BV 1.8 mg/kg Q3Week		BV 2.4 mg/kg Q3Week		BV 1.2 mg/kg Q1Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/46 (52.2%)		13/28 (46.4%)		5/9 (55.6%)
Blood and lymphatic system disorders
Febrile neutropenia	1/46 (2.2%)		0/28 (0%)		1/9 (11.1%)
Lymphopenia	0/46 (0%)		1/28 (3.6%)		0/9 (0%)
Systemic mastocytosis	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Cardiac disorders
Atrial fibrillation	1/46 (2.2%)		0/28 (0%)		1/9 (11.1%)
Atrial flutter	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Cardiac arrest	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Cardiac failure congestive	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Gastrointestinal disorders
Abdominal hernia	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Abdominal pain	3/46 (6.5%)		2/28 (7.1%)		0/9 (0%)
Diarrhea	1/46 (2.2%)		1/28 (3.6%)		1/9 (11.1%)
Dysphagia	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Pancreatitis	0/46 (0%)		1/28 (3.6%)		0/9 (0%)
Small intestinal obstruction	1/46 (2.2%)		1/28 (3.6%)		0/9 (0%)
Stomatitis	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Vomiting	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
General disorders
Fatigue	1/46 (2.2%)		1/28 (3.6%)		0/9 (0%)
Pyrexia	1/46 (2.2%)		1/28 (3.6%)		1/9 (11.1%)
Hepatobiliary disorders
Hepatic failure	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Hepatosplenomegaly	0/46 (0%)		1/28 (3.6%)		0/9 (0%)
Infections and infestations
Bacterial sepsis	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Diverticulitis	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Escherichia sepsis	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Pneumonia	2/46 (4.3%)		1/28 (3.6%)		1/9 (11.1%)
Sepsis	3/46 (6.5%)		0/28 (0%)		0/9 (0%)
Urinary tract infection	1/46 (2.2%)		2/28 (7.1%)		0/9 (0%)
Injury, poisoning and procedural complications
Vascular pseudoaneurysm	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Metabolism and nutrition disorders
Dehydration	2/46 (4.3%)		0/28 (0%)		1/9 (11.1%)
Fluid retention	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Hyperglycemia	0/46 (0%)		1/28 (3.6%)		0/9 (0%)
Hyponatremia	0/46 (0%)		1/28 (3.6%)		0/9 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukemia	0/46 (0%)		2/28 (7.1%)		1/9 (11.1%)
Erythroleukemia	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Malignant pleural effusion	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Mesothelioma malignant	2/46 (4.3%)		2/28 (7.1%)		0/9 (0%)
Ovarian cancer	1/46 (2.2%)		1/28 (3.6%)		0/9 (0%)
Rhabdomyosarcoma	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Nervous system disorders
Dizziness	0/46 (0%)		1/28 (3.6%)		0/9 (0%)
Seizure	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Psychiatric disorders
Mental status changes	0/46 (0%)		1/28 (3.6%)		0/9 (0%)
Renal and urinary disorders
Acute kidney injury	2/46 (4.3%)		0/28 (0%)		0/9 (0%)
Azotemia	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Renal failure	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Renal tubular necrosis	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Dyspnea	2/46 (4.3%)		1/28 (3.6%)		0/9 (0%)
Hypoxia	3/46 (6.5%)		0/28 (0%)		0/9 (0%)
Lung infiltration	0/46 (0%)		1/28 (3.6%)		0/9 (0%)
Pleural effusion	2/46 (4.3%)		0/28 (0%)		0/9 (0%)
Pneumonia aspiration	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Respiratory failure	2/46 (4.3%)		1/28 (3.6%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Rash	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Skin mass	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Vascular disorders
Hypotension	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Lymphoedema	1/46 (2.2%)		0/28 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	BV 1.8 mg/kg Q3Week		BV 2.4 mg/kg Q3Week		BV 1.2 mg/kg Q1Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/46 (91.3%)		28/28 (100%)		8/9 (88.9%)
Blood and lymphatic system disorders
Anemia	6/46 (13%)		1/28 (3.6%)		4/9 (44.4%)
Leukocytosis	0/46 (0%)		1/28 (3.6%)		1/9 (11.1%)
Leukopenia	1/46 (2.2%)		2/28 (7.1%)		0/9 (0%)
Neutropenia	2/46 (4.3%)		3/28 (10.7%)		1/9 (11.1%)
Splenomegaly	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Thrombocytopenia	1/46 (2.2%)		0/28 (0%)		3/9 (33.3%)
Cardiac disorders
Sinus tachycardia	1/46 (2.2%)		2/28 (7.1%)		1/9 (11.1%)
Tachycardia	3/46 (6.5%)		2/28 (7.1%)		0/9 (0%)
Gastrointestinal disorders
Abdominal distension	3/46 (6.5%)		2/28 (7.1%)		0/9 (0%)
Abdominal pain	5/46 (10.9%)		3/28 (10.7%)		0/9 (0%)
Ascites	3/46 (6.5%)		2/28 (7.1%)		0/9 (0%)
Constipation	9/46 (19.6%)		7/28 (25%)		1/9 (11.1%)
Diarrhea	14/46 (30.4%)		5/28 (17.9%)		2/9 (22.2%)
Inguinal hernia	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Nausea	13/46 (28.3%)		11/28 (39.3%)		0/9 (0%)
Retching	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Vomiting	11/46 (23.9%)		7/28 (25%)		0/9 (0%)
General disorders
Asthenia	4/46 (8.7%)		0/28 (0%)		0/9 (0%)
Chest pain	1/46 (2.2%)		2/28 (7.1%)		0/9 (0%)
Chills	6/46 (13%)		2/28 (7.1%)		1/9 (11.1%)
Fatigue	26/46 (56.5%)		10/28 (35.7%)		3/9 (33.3%)
Malaise	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Non-cardiac chest pain	0/46 (0%)		2/28 (7.1%)		0/9 (0%)
Edema peripheral	4/46 (8.7%)		6/28 (21.4%)		1/9 (11.1%)
Pain	2/46 (4.3%)		0/28 (0%)		2/9 (22.2%)
Pyrexia	6/46 (13%)		4/28 (14.3%)		0/9 (0%)
Hepatobiliary disorders
Cholelithiasis	1/46 (2.2%)		0/28 (0%)		1/9 (11.1%)
Infections and infestations
Bronchitis	3/46 (6.5%)		0/28 (0%)		0/9 (0%)
Skin infection	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Urinary tract infection	0/46 (0%)		2/28 (7.1%)		0/9 (0%)
Injury, poisoning and procedural complications
Fall	1/46 (2.2%)		0/28 (0%)		1/9 (11.1%)
Investigations
Alanine aminotransferase increased	0/46 (0%)		2/28 (7.1%)		1/9 (11.1%)
Aspartate aminotransferase increased	0/46 (0%)		2/28 (7.1%)		1/9 (11.1%)
Weight decreased	2/46 (4.3%)		4/28 (14.3%)		0/9 (0%)
Metabolism and nutrition disorders
Decreased appetite	11/46 (23.9%)		9/28 (32.1%)		2/9 (22.2%)
Dehydration	4/46 (8.7%)		3/28 (10.7%)		0/9 (0%)
Hyperkalemia	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Hyperphosphatemia	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Hypokalemia	3/46 (6.5%)		4/28 (14.3%)		1/9 (11.1%)
Hypomagnesemia	1/46 (2.2%)		3/28 (10.7%)		2/9 (22.2%)
Hypophosphatemia	0/46 (0%)		3/28 (10.7%)		1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/46 (8.7%)		3/28 (10.7%)		0/9 (0%)
Back pain	4/46 (8.7%)		5/28 (17.9%)		0/9 (0%)
Flank pain	1/46 (2.2%)		2/28 (7.1%)		0/9 (0%)
Muscular weakness	2/46 (4.3%)		2/28 (7.1%)		1/9 (11.1%)
Musculoskeletal chest pain	0/46 (0%)		1/28 (3.6%)		1/9 (11.1%)
Myalgia	1/46 (2.2%)		4/28 (14.3%)		0/9 (0%)
Myositis	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Nervous system disorders
Dizziness	5/46 (10.9%)		4/28 (14.3%)		0/9 (0%)
Headache	5/46 (10.9%)		3/28 (10.7%)		0/9 (0%)
Peripheral motor neuropathy	5/46 (10.9%)		2/28 (7.1%)		0/9 (0%)
Peripheral sensory neuropathy	8/46 (17.4%)		7/28 (25%)		1/9 (11.1%)
Psychiatric disorders
Anxiety	4/46 (8.7%)		2/28 (7.1%)		0/9 (0%)
Delirium	0/46 (0%)		2/28 (7.1%)		0/9 (0%)
Insomnia	3/46 (6.5%)		4/28 (14.3%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	5/46 (10.9%)		4/28 (14.3%)		1/9 (11.1%)
Dysphonia	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Dyspnea	8/46 (17.4%)		6/28 (21.4%)		3/9 (33.3%)
Dyspnea exertional	3/46 (6.5%)		0/28 (0%)		1/9 (11.1%)
Epistaxis	2/46 (4.3%)		0/28 (0%)		1/9 (11.1%)
Oropharyngeal pain	3/46 (6.5%)		1/28 (3.6%)		0/9 (0%)
Pleural effusion	2/46 (4.3%)		1/28 (3.6%)		1/9 (11.1%)
Pleuritic pain	0/46 (0%)		2/28 (7.1%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Alopecia	6/46 (13%)		7/28 (25%)		2/9 (22.2%)
Hyperhidrosis	3/46 (6.5%)		0/28 (0%)		0/9 (0%)
Pruritus	6/46 (13%)		7/28 (25%)		1/9 (11.1%)
Rash	8/46 (17.4%)		4/28 (14.3%)		0/9 (0%)
Rash maculo-papular	1/46 (2.2%)		3/28 (10.7%)		1/9 (11.1%)
Skin mass	0/46 (0%)		0/28 (0%)		1/9 (11.1%)
Vascular disorders
Flushing	1/46 (2.2%)		4/28 (14.3%)		0/9 (0%)

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 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.