A Phase 3 Trial of Brentuximab Vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Participants With CD30-Positive Cutaneous T-Cell Lymphoma (ALCANZA Study)

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01578499
• Collaborator: Seagen Inc. (Industry)
• Enrollment: 131
• Locations: 41
• Arms: 2
• Actual Duration (Months): 72.8
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine objective response rate (ORR), lasting at least 4 months (ORR4), with brentuximab vedotin in participants with cluster of differentiation antigen 30 positive (CD30+) cutaneous T-cell lymphoma [mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) ]compared to that achieved with therapy in the control arm.

Condition or Disease	Intervention/Treatment	Phase
Primary Cutaneous Anaplastic Large Cell Lymphoma; Mycosis Fungoides; Cutaneous T-Cell Lymphoma	Drug: Brentuximab Vedotin; Drug: Methotrexate; Drug: Bexarotene	Phase 3

Detailed Description

The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat people who have CD30+ cutaneous T-cell lymphoma (mycosis fungoides and primary cutaneous anaplastic large cell lymphoma). This study will look at the overall response of people who took brentuximab vedotin compared to people who took methotrexate or bexarotene as standard care.

The study enrolled 131 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Methotrexate 5 to 50 mg or Bexarotene 300 mg/m^2 (as per physician's choice)

• Brentuximab vedotin 1.8 mg/kg

This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 6 years. Participants will make multiple visits to the clinic every 12 weeks for a minimum of 24 months after the end of treatment (EOT) visit, and then every 6 months until death, study closure, or 6 years after enrollment of the last participant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Phase 3 Trial of Brentuximab Vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T-Cell Lymphoma
• Actual Study Start Date: Jun 11, 2012
• Actual Primary Completion Date: May 31, 2016
• Actual Study Completion Date: Jul 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brentuximab vedotin Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Drug: Brentuximab Vedotin; Brentuximab vedotin intravenous injection.; Other Names: SGN-35
Active Comparator: Methotrexate or Bexarotene Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.	Drug: Methotrexate; Methotrexate tablets.; Drug: Bexarotene; Bexarotene tablets.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4) [Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)]

   ORR4 was determined by an Independent Review Facility (IRF) based on Global Response Score (GRS) which consisted of a skin assessment by the investigator using the modified severity-weighted assessment tool (mSWAT), nodal and visceral radiographic assessment by an IRF and for the participants with mycosis fungoides (MF) only, detection of circulation Sezary cells. Participants whose first response occurred after the start of subsequent anticancer therapy were excluded. Response Criteria was based on International Society for Cutaneous Lymphomas (ISCL), United States Cutaneous Lymphoma Consortium (USCLC) and Cutaneous Lymphoma Task Force (CLTF) of the European Organisation for Research and Treatment of Cancer (EORTC) Consensus guidelines (Olsen, 2011).

Secondary Outcome Measures

1. Percentage of Participants Achieving a CR [Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)]

   Complete Response (CR) was determined by the IRF based on Global Response Score (GRS) which consisted of a skin assessment by the investigator using the modified severity-weighted assessment tool (mSWAT), nodal and visceral radiographic and for the participants with mycosis fungoides (MF) only, detection of circulation Sezary cells. Response Criteria was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).

2. Progression-Free Survival (PFS) [Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)]

   PFS was assessed by the IRF and is defined as the time from randomization until disease progression or death due to any cause, whichever occurs first. Disease progression was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).

3. Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire [Baseline up to End of Treatment (Week 52)]

   Skindex-29 is a 29-item dermatology-specific health-related quality of life (HRQoL). The Skindex-29 incorporates a 28-day recall period and consists of 3 domains: symptoms, emotions, and functioning. The domain scores and an overall score are expressed on a 100-point scale, from 0 to 100 with higher scores indicating lower levels of health- HRQoL. A negative change (reduction) from Baseline indicates improvement.

4. Duration of Response (DOR) [Until disease progression, death or data cutoff (Median follow-up 38.8 months)]

   Duration of response was assessed by the IRF in participants with confirmed response [CR or Partial Response (PR)] and is defined as the time between first documentation of response and disease progression. Response Criteria was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).

5. DOR of Skin Response [Until disease progression, death or data cutoff (Median follow-up 38.8 months)]

   Duration of skin response (CR and PR) was assessed by the investigator and is defined as the time between the first skin response to progressive disease in skin. Per mSWAT, CR is defined as 100% clearance of skin lesions. PR is defined as 50%-99% clearance of skin disease from Baseline; No new tumors in participants without tumors at Baseline -MF; No new tumors-primary cutaneous anaplastic large cell lymphoma (pcALCL).Progressive disease is defined as ≥ 25% increase in skin disease from baseline, or loss of response: in those with CR or PR, increase of skin score of greater than the sum of nadir plus 50% baseline score, or new tumors in participants without tumors at baseline (MF).

6. Event-Free Survival (EFS) [From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)]

   EFS was assessed by the IRF and is defined as the time from randomization until any cause of treatment failure: disease progression, discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. Disease progression was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).

7. Cmax: Maximum Observed Concentration for Brentuximab Vedotin [Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3]

8. Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin [Day 1 pre-dose of Cycles 2 and 4]

9. Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin [Day 1 pre-dose and 30 minutes after infusion ended in Cycles 1 and 3]

10. Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin [Day 1 pre-dose of Cycles 2 and 4]

11. Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin [Baseline up to End of Treatment (Week 52)]

    Blood was collected and evaluated for ATA and neutralizing ATA in all participants who received brentuximab vedotin to assess immunogenicity.

12. Change From Baseline in the Skindex-29 Questionnaire Total Score [Day 1 of Cycles 1, 2, 4, 6, 8, 10, 12, 14, 16, at End of Treatment (EOT) and during posttreatment long treatment follow-up (LTFU) - (Median follow-up 38.8 months)]

    Skindex-29 is a 29-item dermatology-specific health-related quality of life (HRQoL). The Skindex-29 incorporates a 28-day recall period and consists of 3 domains: symptoms, emotions, and functioning. The domain scores and an overall score are expressed on a 100-point scale, 0 to 100 with higher scores indicating lower levels of health- HRQoL. A negative change (reduction) from Baseline indicates improvement.

13. Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score [Day 1 of Cycles 1, 2, 4, 6, 8, 10, 12, 14, 16, at EOT and during posttreatment (LTFU) - (Median follow-up 38.8 months)]

    FACT-G is a 27-item general cancer QOL instrument completed by participants receiving cancer treatment. FACT-G incorporates a 7-day recall period and contains 4 primary subscales: Physical Well-Being (PWB; sum of 7 items, point range 0-28); Social/Family Well-Being (SWB, sum of 7-items, point range 0-28); Emotional Well-Being (EWB; sum of 6-items, point range 0-24); Functional Well-Being (FWB; sum of 7-items, point range 0-28); Fact-G total score=sum of PWB, SWB, EWB, FWB, point range 0-108. Higher scores for the total scales and subscales indicate better quality of life. A negative change (reduction) from Baseline indicates improvement.

14. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [First dose of study drug through 30 days after last dose of study drug (Up to 450 days)]

    AEs and SAEs were assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Voluntary consent form

• Male or female participants 18 years or older with diagnosis of mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL)

• Participants with pcALCL who have received prior radiation therapy or at least 1 prior systemic therapy; participants with MF who have received at least 1 prior systemic therapy

• Histologically confirmed CD30+ disease by central laboratory assessment and pathology review

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant

• Male participants who agree to practice effective barrier contraception or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant

• Clinical laboratory values as specified in protocol

• A 3-week washout period is required from previous treatments (with the exception of a 12-week washout for antibody-directed or immunoglobulin-based immune therapy, or other monoclonal antibody therapies), unless it is not in the best interest of the patient in the opinion of the investigator. Individual cases should be discussed with the project clinician before enrollment.

Exclusion Criteria:

• A concurrent diagnosis of systemic ALCL, or other non Hodgkin lymphoma (excluding LyP) or Sezary syndrome or B2 disease

• Participants with cardiovascular conditions specified in protocols

• Participants with history of another primary malignancy not in remission for at least 3 years

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

• Known human immunodeficiency virus (HIV) infection, hepatitis B or Hepatitis C infection

• Oral retinoid therapy for any indication within 3 weeks of study entry

• Corticosteroid therapy within 3 weeks or immunosuppressive chemotherapy or any antibody-directed or immunoglobulin-based immune therapy (e.g., immunoglobulin replacement, other monoclonal antibody therapies) within 12 weeks of first dose of study drug

• Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 of any cycle

• Previous receipt of brentuximab vedotin Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States
2		Palo Alto	California	United States
3		Chicago	Illinois	United States
4		Boston	Massachusetts	United States
5		Hackensack	New Jersey	United States
6		New York	New York	United States
7		Pittsburgh	Pennsylvania	United States
8		Houston	Texas	United States
9		Concord	New South Wales	Australia
10		South Brisbane	Queensland	Australia
11		Adelaide	South Australia	Australia
12		Nedlands	Western Australia	Australia
13		East Melbourne		Australia
14		St. Poelten		Austria
15		Wien		Austria
16		Leuven		Belgium
17		Sao Paulo		Brazil
18		Nantes Cedex 01		France
19		Paris		France
20		Pessac Cedex		France
21		Pierre Benite		France
22		Reims		France
23		Kiel		Germany
24		Krefeld		Germany
25		Mainz		Germany
26		Mannheim		Germany
27		Minden		Germany
28		Wurzburg		Germany
29		Bologna		Italy
30		Firenze		Italy
31		Meldola		Italy
32		Warszawa		Poland
33		Pamplona	Navarra	Spain
34		Barcelona		Spain
35		Madrid		Spain
36		Zurich		Switzerland
37		Leeds	West Yorkshire	United Kingdom
38		Birmingham		United Kingdom
39		Glasgow		United Kingdom
40		London		United Kingdom
41		Manchester		United Kingdom

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.
• Seagen Inc.

Investigators

• Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Statistical Analysis Plan - May 25, 2016
• Study Protocol - Dec 2, 2014

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01578499
• Other Study ID Numbers: C25001; 2010-024215-14
• First Posted: Apr 17, 2012
• Last Update Posted: Jan 5, 2021
• Last Verified: Dec 1, 2020

• 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 Millennium Pharmaceuticals, Inc.: Brentuximab vedotin; ALCANZA
• Additional relevant MeSH terms: Mycoses; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Mycosis Fungoides; Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell, Cutaneous; Lymphoma, Primary Cutaneous Anaplastic Large Cell; Methotrexate; Brentuximab Vedotin; Bexarotene

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 34 investigative sites in Australia, Belgium, Brazil, France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom, United States from 11 June 2012 to the Primary Completion data of 06 July 2018.
Pre-assignment Detail	Participants with a diagnosis of cluster of differentiation antigen 30 (CD30)-Positive Cutaneous T-Cell Lymphoma were enrolled equally in 1 of 2 arms: brentuximab vedotin 1.8 mg/kg or physician's choice (Methotrexate or Bexarotene).

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Period Title: Overall Study
STARTED	66	65
Safety Population: Treated	66	62
Intent to Treat Population: CD30+	64	64
COMPLETED	32	22
NOT COMPLETED	34	43

Baseline Characteristics

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene	Total
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.	Total of all reporting groups
Overall Participants	66	64	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.4 (13.80)	56.6 (14.43)	58.0 (14.12)
Sex: Female, Male (Count of Participants)
Female	33 50%	28 43.8%	61 46.9%
Male	33 50%	34 53.1%	67 51.5%
Race/Ethnicity, Customized (participants) [Number]
White	56 84.8%	53 82.8%	109 83.8%
Black or African American	3 4.5%	3 4.7%	6 4.6%
Asian	1 1.5%	5 7.8%	6 4.6%
Not reported	3 4.5%	1 1.6%	4 3.1%
Other	1 1.5%	2 3.1%	3 2.3%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	2 3%	6 9.4%	8 6.2%
Not Hispanic or Latino	60 90.9%	50 78.1%	110 84.6%
Not reported	2 3%	8 12.5%	10 7.7%
Region of Enrollment (Count of Participants)
Australia	12 18.2%	8 12.5%	20 15.4%
Belgium	4 6.1%	2 3.1%	6 4.6%
France	4 6.1%	3 4.7%	7 5.4%
Germany	3 4.5%	2 3.1%	5 3.8%
Italy	12 18.2%	6 9.4%	18 13.8%
Poland	2 3%	1 1.6%	3 2.3%
Spain	2 3%	3 4.7%	5 3.8%
Switzerland	3 4.5%	3 4.7%	6 4.6%
United Kingdom	8 12.1%	15 23.4%	23 17.7%
United States	14 21.2%	17 26.6%	31 23.8%
Brazil	2 3%	2 3.1%	4 3.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4)
Description	ORR4 was determined by an Independent Review Facility (IRF) based on Global Response Score (GRS) which consisted of a skin assessment by the investigator using the modified severity-weighted assessment tool (mSWAT), nodal and visceral radiographic assessment by an IRF and for the participants with mycosis fungoides (MF) only, detection of circulation Sezary cells. Participants whose first response occurred after the start of subsequent anticancer therapy were excluded. Response Criteria was based on International Society for Cutaneous Lymphomas (ISCL), United States Cutaneous Lymphoma Consortium (USCLC) and Cutaneous Lymphoma Task Force (CLTF) of the European Organisation for Research and Treatment of Cancer (EORTC) Consensus guidelines (Olsen, 2011).
Time Frame	Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	64	64
Number (95% Confidence Interval) [percentage of participants]	54.7 82.9%	12.5 19.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brentuximab Vedotin, Methotrexate or Bexarotene
	Comments	Based on a two-sided Χ² test with a significance level of 0.05, and a 10% dropout rate, a sample size of approximately 124 participants was calculated to provide 90% power to detect a 30% improvement in ORR4 in the brentuximab vedotin group.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value was stratified by baseline disease diagnosis (pcALCL and MF).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	42.2
	Confidence Interval	(2-Sided) 95%; 27.5 to 56.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Achieving a CR
Description	Complete Response (CR) was determined by the IRF based on Global Response Score (GRS) which consisted of a skin assessment by the investigator using the modified severity-weighted assessment tool (mSWAT), nodal and visceral radiographic and for the participants with mycosis fungoides (MF) only, detection of circulation Sezary cells. Response Criteria was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).
Time Frame	Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	64	64
Number (95% Confidence Interval) [percentage of participants]	17.2 26.1%	1.6 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brentuximab Vedotin, Methotrexate or Bexarotene
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-value was stratified by baseline disease diagnosis (pcALCL and MF).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.6
	Confidence Interval	(2-Sided) 95%; -2.5 to 33.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was assessed by the IRF and is defined as the time from randomization until disease progression or death due to any cause, whichever occurs first. Disease progression was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).
Time Frame	Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	64	64
Median (95% Confidence Interval) [months]	16.7	3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brentuximab Vedotin, Methotrexate or Bexarotene
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.378
	Confidence Interval	(2-Sided) 95%; 0.247 to 0.577
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Hazard ratio brentuximab vedotin/ comparator (methotrexate or bexarotene) with the 95% CI from a stratified Cox regression model with treatment as the explanatory variable and baseline disease diagnosis (MF or pcALCL) as stratification factor.

4. Secondary Outcome

Title	Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire
Description	Skindex-29 is a 29-item dermatology-specific health-related quality of life (HRQoL). The Skindex-29 incorporates a 28-day recall period and consists of 3 domains: symptoms, emotions, and functioning. The domain scores and an overall score are expressed on a 100-point scale, from 0 to 100 with higher scores indicating lower levels of health- HRQoL. A negative change (reduction) from Baseline indicates improvement.
Time Frame	Baseline up to End of Treatment (Week 52)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Here number of participants analyzed are participants evaluable for this outcome measure.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	58	54
Mean (Standard Deviation) [score on a scale]	-28.08 (26.863)	-8.62 (17.013)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brentuximab Vedotin, Methotrexate or Bexarotene
	Comments	P-value is calculated using the analysis of covariance (ANCOVA) model controlling for baseline symptom domain score, eastern cooperative oncology group (ECOG) performance status score (=0 and ≥1), and disease diagnosis (pcALCL and MF) between the brentuximab vedotin and comparator (methotrexate or bexarotene) arms.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimate of difference
	Estimated Value	-19.0
	Confidence Interval	(2-Sided) 95%; -26.7 to -11.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Duration of Response (DOR)
Description	Duration of response was assessed by the IRF in participants with confirmed response [CR or Partial Response (PR)] and is defined as the time between first documentation of response and disease progression. Response Criteria was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).
Time Frame	Until disease progression, death or data cutoff (Median follow-up 38.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Responders in ITT population were analyzed in this outcome measure.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	42	13
Median (95% Confidence Interval) [months]	15.1	18.4

6. Secondary Outcome

Title	DOR of Skin Response
Description	Duration of skin response (CR and PR) was assessed by the investigator and is defined as the time between the first skin response to progressive disease in skin. Per mSWAT, CR is defined as 100% clearance of skin lesions. PR is defined as 50%-99% clearance of skin disease from Baseline; No new tumors in participants without tumors at Baseline -MF; No new tumors-primary cutaneous anaplastic large cell lymphoma (pcALCL).Progressive disease is defined as ≥ 25% increase in skin disease from baseline, or loss of response: in those with CR or PR, increase of skin score of greater than the sum of nadir plus 50% baseline score, or new tumors in participants without tumors at baseline (MF).
Time Frame	Until disease progression, death or data cutoff (Median follow-up 38.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Skin responders in ITT population were analyzed in this outcome measure.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	47	19
Median (95% Confidence Interval) [months]	18.9	18.3

7. Secondary Outcome

Title	Event-Free Survival (EFS)
Description	EFS was assessed by the IRF and is defined as the time from randomization until any cause of treatment failure: disease progression, discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. Disease progression was based on ISCL, USCLC and CLTF of the EORTC Consensus guidelines (Olsen, 2011).
Time Frame	From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	64	64
Median (95% Confidence Interval) [months]	9.4	2.3

8. Secondary Outcome

Title	Cmax: Maximum Observed Concentration for Brentuximab Vedotin
Time Frame	Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Arm/Group Title	pcALCL: Brentuximab Vedotin	MF: Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants with primary cutaneous anaplastic large cell lymphoma (pcALCL) received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Participants with mycosis fungoides (MF) received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).
Measure Participants	16	50
Cycle 1 Day 1	38.36 (9.427)	38.40 (8.912)
Cycle 3 Day 1	40.14 (12.697)	36.69 (14.249)

9. Secondary Outcome

Title	Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin
Time Frame	Day 1 pre-dose of Cycles 2 and 4

Outcome Measure Data

Analysis Population Description

The PK population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Arm/Group Title	pcALCL: Brentuximab Vedotin	MF: Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants with pcALCL received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Participants with MF received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).
Measure Participants	16	50
Cycle 2 Day 1	3.57 (10.101)	0.58 (0.517)
Cycle 4 Day 1	0.99 (0.528)	0.78 (0.446)

10. Secondary Outcome

Title	Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin
Time Frame	Day 1 pre-dose and 30 minutes after infusion ended in Cycles 1 and 3

Outcome Measure Data

Analysis Population Description

The PK population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Arm/Group Title	pcALCL: Brentuximab Vedotin	MF: Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants with pcALCL received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Participants with MF received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).
Measure Participants	16	50
Cycle 1 Day 1	2.53 (1.382)	3.34 (1.901)
Cycle 3 Day 1	2.96 (1.176)	3.08 (1.276)

11. Secondary Outcome

Title	Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin
Time Frame	Day 1 pre-dose of Cycles 2 and 4

Outcome Measure Data

Analysis Population Description

The PK population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Arm/Group Title	pcALCL: Brentuximab Vedotin	MF: Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants with pcALCL received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Participants with MF received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).
Measure Participants	16	50
Cycle 2 Day 1	0.11 (0.095)	0.09 (0.060)
Cycle 4 Day 1	0.14 (0.113)	0.11 (0.091)

12. Secondary Outcome

Title	Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin
Description	Blood was collected and evaluated for ATA and neutralizing ATA in all participants who received brentuximab vedotin to assess immunogenicity.
Time Frame	Baseline up to End of Treatment (Week 52)

Outcome Measure Data

Analysis Population Description

The Safety population included participants who received at least one dose of study drug.

Arm/Group Title	pcALCL: Brentuximab Vedotin	MF: Brentuximab Vedotin 1.8 mg/kg
Arm/Group Description	Participants with pcALCL received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Participants with MF received brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).
Measure Participants	16	50
Immunogenicity-evaluable participants	14 21.2%	46 71.9%
Baseline Negative: ATA negative	8 12.1%	23 35.9%
Baseline Negative: ATA positive	6 9.1%	19 29.7%
Baseline Negative: Transiently Positive	4 6.1%	9 14.1%
Baseline Negative: Persistently Positive	2 3%	10 15.6%
Baseline Negative: Neutralizing ATA Positive	4 6.1%	14 21.9%
Baseline Positive: ATA Negative	0 0%	1 1.6%
Baseline Positive: ATA Positive	0 0%	3 4.7%
Baseline Positive: Transiently Positive	0 0%	3 4.7%
Baseline Positive: Persistently Positive	0 0%	0 0%
Baseline Positive: Neutralizing ATA Positive	0 0%	2 3.1%

13. Secondary Outcome

Title	Change From Baseline in the Skindex-29 Questionnaire Total Score
Description	Skindex-29 is a 29-item dermatology-specific health-related quality of life (HRQoL). The Skindex-29 incorporates a 28-day recall period and consists of 3 domains: symptoms, emotions, and functioning. The domain scores and an overall score are expressed on a 100-point scale, 0 to 100 with higher scores indicating lower levels of health- HRQoL. A negative change (reduction) from Baseline indicates improvement.
Time Frame	Day 1 of Cycles 1, 2, 4, 6, 8, 10, 12, 14, 16, at End of Treatment (EOT) and during posttreatment long treatment follow-up (LTFU) - (Median follow-up 38.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	64	64
Change at Cycle 2	-5.44 (11.055)	-2.49 (11.959)
Change at Cycle 4	-14.60 (17.488)	-6.71 (9.755)
Change at Cycle 6	-17.59 (17.770)	-5.40 (9.758)
Change at Cycle 8	-21.73 (18.882)	-7.28 (16.769)
Change at Cycle 10	-22.47 (21.722)	-3.71 (21.752)
Change at Cycle 12	-23.37 (21.555)	-5.22 (17.704)
Change at Cycle 14	-19.72 (20.980)	-7.49 (22.463)
Change at Cycle 16	-19.35 (18.911)	0.75 (10.308)
Change at End of Treatment	-16.26 (23.281)	-0.96 (18.973)
Change at 3-6 months LTFU	-1.07 (3.704)	-9.48 (21.629)
Change at 6-9 months LTFU	-8.04 (8.800)	-9.68 (17.789)
Change at 9-12 months LTFU	-7.94 (15.582)	-4.93 (14.516)
Change at 12-15 months LTFU	-16.21 (18.438)	-11.16 (18.183)
Change at 15-18 months LTFU	-19.18 (19.475)	-8.53 (12.768)
Change at 18-21 months LTFU	-19.27 (20.962)	-5.46 (16.679)
Change at 21-24 months LTFU	-16.60 (19.875)	-6.86 (14.991)
Change at 24-27 months LTFU	-17.04 (15.982)	-9.05 (23.990)
Change at 27-30 months LTFU	-12.45 (19.639)	-7.97 (16.401)
Change at >30 months LTFU	-11.49 (22.470)	-1.07 (18.886)

14. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score
Description	FACT-G is a 27-item general cancer QOL instrument completed by participants receiving cancer treatment. FACT-G incorporates a 7-day recall period and contains 4 primary subscales: Physical Well-Being (PWB; sum of 7 items, point range 0-28); Social/Family Well-Being (SWB, sum of 7-items, point range 0-28); Emotional Well-Being (EWB; sum of 6-items, point range 0-24); Functional Well-Being (FWB; sum of 7-items, point range 0-28); Fact-G total score=sum of PWB, SWB, EWB, FWB, point range 0-108. Higher scores for the total scales and subscales indicate better quality of life. A negative change (reduction) from Baseline indicates improvement.
Time Frame	Day 1 of Cycles 1, 2, 4, 6, 8, 10, 12, 14, 16, at EOT and during posttreatment (LTFU) - (Median follow-up 38.8 months)

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	64	64
Change at Cycle 2	1.43 (10.168)	-0.37 (11.723)
Change at Cycle 4	1.75 (12.014)	1.78 (10.740)
Change at Cycle 6	4.23 (14.257)	2.24 (13.108)
Change at Cycle 8	5.96 (16.030)	2.54 (10.809)
Change at Cycle 10	6.61 (16.971)	4.38 (15.040)
Change at Cycle 12	7.94 (18.837)	8.61 (21.024)
Change at Cycle 14	9.04 (14.104)	10.75 (13.615)
Change at Cycle 16	5.08 (9.230)	7.88 (23.432)
Change at End of Treatment	0.35 (16.067)	-2.29 (17.171)
Change at 3-6 months LTFU	16.00 (18.385)	-2.92 (8.367)
Change at 6-9 months LTFU	-0.19 (19.648)	-2.59 (12.473)
Change at 9-12 months LTFU	3.62 (17.651)	-5.32 (10.555)
Change at 12-15 months LTFU	8.33 (14.918)	-1.34 (11.905)
Change at 15-18 months LTFU	3.03 (12.618)	2.94 (14.756)
Change at 18-21 months LTFU	3.35 (11.117)	-0.19 (14.316)
Change at 21-24 months LTFU	1.51 (5.471)	0.61 (14.505)
Change at 24-27 months LTFU	4.20 (7.952)	1.42 (17.870)
Change at 27-30 months LTFU	-1.57 (17.488)	1.93 (8.716)
Change at >30 months LTFU	-6.22 (15.222)	-2.85 (5.518)

15. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	AEs and SAEs were assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event.
Time Frame	First dose of study drug through 30 days after last dose of study drug (Up to 450 days)

Outcome Measure Data

Analysis Population Description

The Safety population included participants who received at least one dose of study drug.

Arm/Group Title	Brentuximab Vedotin	Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).	Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
Measure Participants	66	62
AEs	63 95.5%	56 87.5%
SAEs	18 27.3%	18 28.1%

Adverse Events

Time Frame	All-Cause mortality: Baseline up to End of study (Up to 6 years); Serious and Other adverse events: First dose of study drug through 30 days after last dose of study drug (Up to 450 days)
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.
Arm/Group Title	Brentuximab Vedotin		Methotrexate or Bexarotene
Arm/Group Description	Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).		Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
All Cause Mortality
	Brentuximab Vedotin		Methotrexate or Bexarotene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/66 (33.3%)		25/62 (40.3%)
Serious Adverse Events
	Brentuximab Vedotin		Methotrexate or Bexarotene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/66 (27.3%)		18/62 (29%)
Blood and lymphatic system disorders
Haemolytic uraemic syndrome	1/66 (1.5%)		0/62 (0%)
Gastrointestinal disorders
Pancreatitis	1/66 (1.5%)		0/62 (0%)
Diarrhoea	1/66 (1.5%)		0/62 (0%)
Intestinal perforation	1/66 (1.5%)		0/62 (0%)
General disorders
Pyrexia	2/66 (3%)		4/62 (6.5%)
Extravasation	1/66 (1.5%)		0/62 (0%)
General physical health deterioration	1/66 (1.5%)		0/62 (0%)
Multiple organ dysfunction syndrome	1/66 (1.5%)		0/62 (0%)
Fatigue	1/66 (1.5%)		0/62 (0%)
Hepatobiliary disorders
Hepatocellular injury	1/66 (1.5%)		0/62 (0%)
Infections and infestations
Cellulitis	2/66 (3%)		0/62 (0%)
Superinfection bacterial	0/66 (0%)		1/62 (1.6%)
Diverticulitis	1/66 (1.5%)		0/62 (0%)
Lower respiratory tract infection	1/66 (1.5%)		0/62 (0%)
Sepsis	1/66 (1.5%)		3/62 (4.8%)
Urosepsis	0/66 (0%)		1/62 (1.6%)
Impetigo	1/66 (1.5%)		0/62 (0%)
Sinusitis	1/66 (1.5%)		0/62 (0%)
Urinary tract infection	1/66 (1.5%)		0/62 (0%)
Parotitis	0/66 (0%)		1/62 (1.6%)
Periorbital infection	0/66 (0%)		1/62 (1.6%)
Erysipelas	0/66 (0%)		1/62 (1.6%)
Skin infection	0/66 (0%)		1/62 (1.6%)
Injury, poisoning and procedural complications
Fracture	1/66 (1.5%)		0/62 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/66 (1.5%)		0/62 (0%)
Hypernatraemia	0/66 (0%)		1/62 (1.6%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/66 (1.5%)		0/62 (0%)
Neck pain	1/66 (1.5%)		0/62 (0%)
Crystal arthropathy	0/66 (0%)		1/62 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma	1/66 (1.5%)		0/62 (0%)
Squamous cell carcinoma of skin	0/66 (0%)		1/62 (1.6%)
Nervous system disorders
Dizziness	1/66 (1.5%)		0/62 (0%)
Neuropathy peripheral	1/66 (1.5%)		0/62 (0%)
Neuralgia	0/66 (0%)		1/62 (1.6%)
Psychiatric disorders
Stress	1/66 (1.5%)		0/62 (0%)
Renal and urinary disorders
Urinary retention	1/66 (1.5%)		0/62 (0%)
Haematuria	0/66 (0%)		1/62 (1.6%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/66 (1.5%)		0/62 (0%)
Skin and subcutaneous tissue disorders
Drug eruption	1/66 (1.5%)		0/62 (0%)
Rash maculo-papular	1/66 (1.5%)		0/62 (0%)
Dermatitis bullous	0/66 (0%)		1/62 (1.6%)
Skin erosion	0/66 (0%)		1/62 (1.6%)
Vascular disorders
Hypotension	1/66 (1.5%)		0/62 (0%)
Peripheral vascular disorder	0/66 (0%)		1/62 (1.6%)
Peripheral ischaemia	0/66 (0%)		1/62 (1.6%)
Other (Not Including Serious) Adverse Events
	Brentuximab Vedotin		Methotrexate or Bexarotene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/66 (90.9%)		51/62 (82.3%)
Blood and lymphatic system disorders
Neutropenia	5/66 (7.6%)		4/62 (6.5%)
Anaemia	3/66 (4.5%)		6/62 (9.7%)
Endocrine disorders
Hypothyroidism	0/66 (0%)		5/62 (8.1%)
Eye disorders
Dry eye	0/66 (0%)		4/62 (6.5%)
Gastrointestinal disorders
Nausea	24/66 (36.4%)		9/62 (14.5%)
Vomiting	11/66 (16.7%)		3/62 (4.8%)
Diarrhoea	18/66 (27.3%)		4/62 (6.5%)
Constipation	3/66 (4.5%)		5/62 (8.1%)
General disorders
Fatigue	18/66 (27.3%)		18/62 (29%)
Asthenia	7/66 (10.6%)		5/62 (8.1%)
Pyrexia	9/66 (13.6%)		8/62 (12.9%)
Oedema peripheral	7/66 (10.6%)		6/62 (9.7%)
Chills	4/66 (6.1%)		2/62 (3.2%)
Peripheral swelling	1/66 (1.5%)		4/62 (6.5%)
Infections and infestations
Upper respiratory tract infection	4/66 (6.1%)		2/62 (3.2%)
Skin infection	2/66 (3%)		6/62 (9.7%)
Urinary tract infection	4/66 (6.1%)		4/62 (6.5%)
Staphylococcal skin infection	1/66 (1.5%)		5/62 (8.1%)
Investigations
Weight decreased	6/66 (9.1%)		2/62 (3.2%)
Alanine aminotransferase increased	3/66 (4.5%)		5/62 (8.1%)
Aspartate aminotransferase increased	1/66 (1.5%)		4/62 (6.5%)
Blood cholesterol increased	0/66 (0%)		4/62 (6.5%)
Blood triglycerides increased	0/66 (0%)		5/62 (8.1%)
Metabolism and nutrition disorders
Decreased appetite	10/66 (15.2%)		3/62 (4.8%)
Hyperglycaemia	5/66 (7.6%)		0/62 (0%)
Hyperuricaemia	4/66 (6.1%)		2/62 (3.2%)
Hypertriglyceridaemia	1/66 (1.5%)		11/62 (17.7%)
Hypercholesterolaemia	0/66 (0%)		4/62 (6.5%)
Musculoskeletal and connective tissue disorders
Pain in extremity	6/66 (9.1%)		4/62 (6.5%)
Arthralgia	8/66 (12.1%)		4/62 (6.5%)
Myalgia	8/66 (12.1%)		2/62 (3.2%)
Muscle spasms	4/66 (6.1%)		3/62 (4.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/66 (1.5%)		5/62 (8.1%)
Nervous system disorders
Peripheral sensory neuropathy	31/66 (47%)		1/62 (1.6%)
Peripheral motor neuropathy	4/66 (6.1%)		0/62 (0%)
Paraesthesia	6/66 (9.1%)		1/62 (1.6%)
Dysgeusia	5/66 (7.6%)		0/62 (0%)
Headache	5/66 (7.6%)		6/62 (9.7%)
Dizziness	4/66 (6.1%)		1/62 (1.6%)
Psychiatric disorders
Insomnia	2/66 (3%)		6/62 (9.7%)
Anxiety	0/66 (0%)		4/62 (6.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	7/66 (10.6%)		0/62 (0%)
Cough	2/66 (3%)		4/62 (6.5%)
Skin and subcutaneous tissue disorders
Alopecia	10/66 (15.2%)		2/62 (3.2%)
Rash maculo-papular	7/66 (10.6%)		3/62 (4.8%)
Urticaria	5/66 (7.6%)		1/62 (1.6%)
Dry skin	1/66 (1.5%)		4/62 (6.5%)
Pruritus	11/66 (16.7%)		8/62 (12.9%)
Pruritus generalised	7/66 (10.6%)		1/62 (1.6%)
Vascular disorders
Hypertension	6/66 (9.1%)		0/62 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.