Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma

• Sponsor: Takeda (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01909934
• Collaborator: Takeda Development Center Americas, Inc. (Industry)
• Enrollment: 50
• Locations: 40
• Arm: 1
• Anticipated Duration (Months): 128.1
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a single-arm, open-label, multicenter, phase 4 clinical trial to evaluate the efficacy and safety of brentuximab vedotin as a single agent in participants with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).

Condition or Disease	Intervention/Treatment	Phase
Anaplastic Large-cell Lymphoma	Drug: brentuximab vedotin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 4, Open-label, Single-Arm Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma
• Actual Study Start Date: Jan 30, 2014
• Actual Primary Completion Date: May 4, 2021
• Anticipated Study Completion Date: Oct 4, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brentuximab vedotin 1.8 mg/kg IV infusion	Drug: brentuximab vedotin; Brentuximab vedotin will be administered as a single intravenous (IV) infusion over 30 minutes on Day 1 of each 3 week cycle for up to a maximum of 16 cycles and should be administered for a minimum of 8 cycles for participants who achieve stable disease or better.; Other Names: SGN-35 ADCETRIS

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [Up to data cut-off date: 04 May 2021 (Up to approximately 7 years)]

   ORR was defined as the percentage of participants with a complete remission (CR) or partial remission (PR) by Independent Review Facility (IRF) response assessment according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.

Secondary Outcome Measures

1. Duration of Response (DOR) as Per IRF [Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)]

   DOR was defined as the time between initial response and documented tumor progression in the subset of participants who achieved an objective response, either CR or PR. DOR per IRF was based upon the radiological assessment of measured lesions from an independent review facility. DOR was censored on the date of the last disease assessment documenting absence of progressive disease (PD) for participants who were lost to follow-up, withdrew consent, started a new anticancer therapy other than SCT, or discontinued treatment due to undocumented PD after the last adequate disease assessment.

2. Progression-free Survival (PFS) as Per IRF [Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)]

   PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. PFS per IRF is based upon the radiological assessment from an independent review facility.

3. Complete Remission Rate (CRR) [Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)]

   CRR is defined as percentage of participants with CR. CR is defined as the disappearance of all evidence of disease.

4. Overall Survival (OS) [Until death or the data cut-off date: 4 May 2021 (Up to approximately 7 years)]

   OS is defined as the time from start of study treatment to date of death due to any cause.

5. Percentage of Participants Receiving Hematopoietic Stem Cell Transplant (SCT) Following Treatment With Brentuximab Vedotin [Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)]

6. Percentage of Participants With Adverse Events (AEs), Serious Adverse Events, Related Adverse Events and Adverse Events by Severity (Grade 3 or Higher) [From first dose up to 30 days post last dose of study drug (Up to approximately 17 months)]

   An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. Serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is a medically important event.

7. Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion [Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion]

8. Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody [Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion]

9. Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE) [Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion]

10. Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antidrug Antibody (Nab) to Brentuximab Vedotin [Up to 16 cycles (each cycle = 21 days)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female participants age 18 years or older, with relapsed or refractory sALCL who have previously received at least 1 multiagent chemotherapy

• Bidimensional measurable disease

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug, or agree to practice true abstinence

• Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence

• Clinical laboratory values as specified in the study protocol

Exclusion Criteria:

• Previous treatment with brentuximab vedotin.

• Previously received an allogeneic transplant.

• Participants with current diagnosis of primary cutaneous anaplastic large cell lymphoma [ALCL] (participants whose ALCL has transformed to sALCL are eligible).

• Known cerebral/meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy (PML)

• Female participants who are lactating and breastfeeding or pregnant

• Known human immunodeficiency virus (HIV) positive

• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ZNA Stuivenberg	Antwerpen		Belgium	2060
2	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
3	Universitair Ziekenhuis Gent	Gent		Belgium	9000
4	UZ Leuven	Leuven		Belgium	3000
5	Clinical Hospital Centre Rijeka	Rijeka		Croatia	51000
6	Clinical Hospital Centre Zagreb	Zagreb		Croatia	10000
7	Clinical Hospital Dubrava	Zagreb		Croatia	10000
8	Fakultni nemocnice Brno	Brno		Czechia	625 00
9	Fakultni nemocnice Olomouc	Olomouc		Czechia	779 00
10	Fakultni nemocnice Kralovske Vinohrady	Praha 10		Czechia	100 34
11	Vseobecna fakultni nemocnice v Praze	Praha 2		Czechia	128 08
12	Semmelweis Egyetem	Budapest		Hungary	1083
13	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
14	Pecsi Tudomanyegyetem	Pecs		Hungary	7624
15	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
16	Malopolskie Centrum Medyczne s.c.	Krakow		Poland	30-510
17	SPZOZ MSW zWarminsko-MazurskimCen.Onko.wOlsztynie	Olsztyn		Poland	10-228
18	Centrum Onkologii-Instytut im. M. Sklodowskiej Curie	Warszawa		Poland	02-781
19	Hospital de Braga	Braga		Portugal	4710-243
20	Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria	Lisboa		Portugal	1649-035
21	Centro Hospitalar do Porto, E.P.E. - Hospital de Santo Antonio	Porto		Portugal	4099-001
22	Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE	Porto		Portugal	4200-072
23	Policlinica de Diagnostic Rapid SA	Brasov		Romania	500152
24	Spitalul Clinic Colentina	Bucuresti		Romania	020125
25	Spitalul Clinic Coltea	Bucuresti		Romania	030171
26	Spitalul Clinic Judetean de Urgenta Targu Mures	Targu Mures		Romania	540042
27	ICO lHospitalet Hospital Duran i Reynals	L'Hospitalet de Llobregat	Barcelona	Spain	08907
28	Hospital Universitario Marques de Valdecilla	Santander	Cantabria	Spain	39008
29	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
30	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
31	Hospital Universitario de Salamanca	Salamanca		Spain	37007
32	Ankara University Medical Faculty	Ankara		Turkey	06340
33	Pamukkale Uni. Med. Fac.	Denizli		Turkey	20070
34	Istanbul Bilim University Medical Fac.	Istanbul		Turkey	34200
35	Ege University Medical Faculty	Izmir		Turkey	35040
36	Dokuz Eylul University Faculty of Medicine	Izmir		Turkey	35340
37	Erciyes University Medical Faculty	Kayseri		Turkey	38039
38	Royal Cornwall Hospital	Truro	Cornwall	United Kingdom	TR1 3LJ
39	The Christie	Manchester	Greater Manchester	United Kingdom	M20 4BX
40	Birmingham Heartlands Hospital	Birmingham	West Midlands	United Kingdom	B9 5SS

Sponsors and Collaborators

• Takeda
• Takeda Development Center Americas, Inc.

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Aug 27, 2021
• Statistical Analysis Plan - Jun 18, 2021

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01909934
• Other Study ID Numbers: C25006; 2012-004128-39; U1111-1154-9784; REec-2014-0649; 13/NI/0072
• First Posted: Jul 29, 2013
• Last Update Posted: May 26, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Lymphoma; Anaplastic Large-cell; Relapsed; Refractory; Antigens, CD30; Antibody-Drug Conjugate; Antibodies, Monoclonal; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Anaplastic; monomethyl auristatin E; Drug Therapy; Immunotherapy; Hematologic Diseases
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Anaplastic; Brentuximab Vedotin

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 24 investigative sites in Belgium, Croatia, Czech Republic, Hungary, Poland, Portugal, Romania, Spain, Turkey, and United Kingdom from 23 January 2014 to data cut-off: 04 May 2021. This study is ongoing.
Pre-assignment Detail	Participants with a diagnosis of relapsed or refractory systemic anaplastic large cell lymphoma were enrolled in single arm to receive brentuximab vedotin 1.8 mg/kg.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Period Title: Overall Study
STARTED	50
COMPLETED	0
NOT COMPLETED	50

Baseline Characteristics

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Overall Participants	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.4 (16.70)
Sex: Female, Male (Count of Participants)
Female	31 62%
Male	19 38%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4%
Not Hispanic or Latino	45 90%
Unknown or Not Reported	3 6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	50 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Belgium	1 2%
Croatia	2 4%
Czech Republic	12 24%
Hungary	5 10%
Poland	8 16%
Portugal	3 6%
Romania	3 6%
Spain	4 8%
Turkey	6 12%
United Kingdom	6 12%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	166.8 (10.40)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	75.2 (20.73)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.9 (6.39)

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	ORR was defined as the percentage of participants with a complete remission (CR) or partial remission (PR) by Independent Review Facility (IRF) response assessment according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
Time Frame	Up to data cut-off date: 04 May 2021 (Up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population included all participants enrolled in the study.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	50
Number (95% Confidence Interval) [percentage of participants]	64 128%

2. Secondary Outcome

Title	Duration of Response (DOR) as Per IRF
Description	DOR was defined as the time between initial response and documented tumor progression in the subset of participants who achieved an objective response, either CR or PR. DOR per IRF was based upon the radiological assessment of measured lesions from an independent review facility. DOR was censored on the date of the last disease assessment documenting absence of progressive disease (PD) for participants who were lost to follow-up, withdrew consent, started a new anticancer therapy other than SCT, or discontinued treatment due to undocumented PD after the last adequate disease assessment.
Time Frame	Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population included all participants enrolled in the study. Only responders were analyzed for this outcome measure.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	32
Median (95% Confidence Interval) [months]	NA

3. Secondary Outcome

Title	Progression-free Survival (PFS) as Per IRF
Description	PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. PFS per IRF is based upon the radiological assessment from an independent review facility.
Time Frame	Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population included all participants enrolled in the study.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	50
Number (95% Confidence Interval) [months]	20.9

4. Secondary Outcome

Title	Complete Remission Rate (CRR)
Description	CRR is defined as percentage of participants with CR. CR is defined as the disappearance of all evidence of disease.
Time Frame	Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population included all participants enrolled in the study.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	50
Number (95% Confidence Interval) [percentage of participants]	30 60%

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from start of study treatment to date of death due to any cause.
Time Frame	Until death or the data cut-off date: 4 May 2021 (Up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population included all participants enrolled in the study.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	50
Median (95% Confidence Interval) [months]	59.5

6. Secondary Outcome

Title	Percentage of Participants Receiving Hematopoietic Stem Cell Transplant (SCT) Following Treatment With Brentuximab Vedotin
Time Frame	Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population included all participants enrolled in the study.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	50
Number [percentage of participants]	26 52%

7. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs), Serious Adverse Events, Related Adverse Events and Adverse Events by Severity (Grade 3 or Higher)
Description	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. Serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is a medically important event.
Time Frame	From first dose up to 30 days post last dose of study drug (Up to approximately 17 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of brentuximab vedotin.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	50
AE	94 188%
SAE	32 64%
Drug-Related Adverse Event	70 140%
Adverse Events by Severity (Grade 3 or Higher)	58 116%

8. Secondary Outcome

Title	Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion
Time Frame	Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. Overall and number analyzed are participants with data available for analyses at the given timepoint.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	48
Cycle 1, Day 1	35 (35)
Cycle 3, Day 1	38 (25)

9. Secondary Outcome

Title	Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody
Time Frame	Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. Overall and number analyzed are participants with data available for analyses at the given timepoint.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	48
Cycle 1, Day 1	33 (29)
Cycle 3, Day 1	38 (23)

10. Secondary Outcome

Title	Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE)
Time Frame	Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. Overall and number analyzed are participants with data available for analyses at the given timepoint.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	49
Cycle 1, Day 1	0.25 (87)
Cycle 3, Day 1	0.29 (88)

11. Secondary Outcome

Title	Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antidrug Antibody (Nab) to Brentuximab Vedotin
Time Frame	Up to 16 cycles (each cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. Overall number analyzed are participants with data available for analyses at the given timepoint.

Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
Measure Participants	44
ATA Positive	30 60%
Neutralizing ATA Positive	0.0 0%

Adverse Events

Time Frame	All-cause mortality: Up to data cut-off date: 4 May 2021 (Up to approximately 7 years); Serious and other adverse events: From the first dose of study drug up to 30 days after the last dose of study drug (Up to 17 months)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population included all participants who received at least 1 dose of brentuximab vedotin.
Arm/Group Title	Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles.
All Cause Mortality
	Brentuximab Vedotin 1.8 mg/kg
	Affected / at Risk (%)	# Events
Total	22/50 (44%)
Serious Adverse Events
	Brentuximab Vedotin 1.8 mg/kg
	Affected / at Risk (%)	# Events
Total	16/50 (32%)
Blood and lymphatic system disorders
Neutropenia	1/50 (2%)
Cardiac disorders
Cardiac failure acute	1/50 (2%)
Gastrointestinal disorders
Diarrhoea	2/50 (4%)
Abdominal incarcerated hernia	1/50 (2%)
Colitis	1/50 (2%)
Large intestinal haemorrhage	1/50 (2%)
Small intestinal perforation	1/50 (2%)
Haematemesis	1/50 (2%)
Upper gastrointestinal haemorrhage	1/50 (2%)
General disorders
General physical health deterioration	2/50 (4%)
Death	1/50 (2%)
Infections and infestations
Pneumonia	2/50 (4%)
Epididymitis	1/50 (2%)
Metabolism and nutrition disorders
Decreased appetite	1/50 (2%)
Malnutrition	1/50 (2%)
Hypokalaemia	1/50 (2%)
Dehydration	1/50 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anaplastic large-cell lymphoma	2/50 (4%)
Invasive lobular breast carcinoma	1/50 (2%)
Nervous system disorders
Central nervous system haemorrhage	1/50 (2%)
Ischaemic stroke	1/50 (2%)
Autonomic neuropathy	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/50 (4%)
Acute respiratory failure	1/50 (2%)
Respiratory failure	1/50 (2%)
Chronic obstructive pulmonary disease	1/50 (2%)
Pneumonitis	1/50 (2%)
Vascular disorders
Hypotension	2/50 (4%)
Aortic stenosis	1/50 (2%)
Other (Not Including Serious) Adverse Events
	Brentuximab Vedotin 1.8 mg/kg
	Affected / at Risk (%)	# Events
Total	37/50 (74%)
Blood and lymphatic system disorders
Neutropenia	8/50 (16%)
Anaemia	7/50 (14%)
Thrombocytopenia	3/50 (6%)
Gastrointestinal disorders
Diarrhoea	8/50 (16%)
Nausea	5/50 (10%)
Constipation	4/50 (8%)
Vomiting	4/50 (8%)
General disorders
Pyrexia	9/50 (18%)
Fatigue	6/50 (12%)
Malaise	3/50 (6%)
Oedema peripheral	3/50 (6%)
Infections and infestations
Upper respiratory tract infection	4/50 (8%)
Metabolism and nutrition disorders
Decreased appetite	4/50 (8%)
Hyponatraemia	3/50 (6%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/50 (10%)
Back pain	4/50 (8%)
Myalgia	3/50 (6%)
Pain in extremity	3/50 (6%)
Nervous system disorders
Peripheral sensory neuropathy	9/50 (18%)
Neuropathy peripheral	4/50 (8%)
Paraesthesia	3/50 (6%)
Peripheral motor neuropathy	3/50 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	4/50 (8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.