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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01578499




Registration number
NCT01578499
Ethics application status
Date submitted
27/03/2012
Date registered
17/04/2012
Date last updated
3/09/2019

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2010-024215-14
Secondary ID [2] 0 0
C25001
Universal Trial Number (UTN)
Trial acronym
ALCANZA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Cutaneous Anaplastic Large Cell Lymphoma 0 0
Mycosis Fungoides 0 0
Cutaneous T-Cell Lymphoma 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Brentuximab Vedotin
Treatment: Drugs - Methotrexate
Treatment: Drugs - Bexarotene

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).

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.


Treatment: Drugs: Brentuximab Vedotin
Brentuximab vedotin intravenous injection.

Treatment: Drugs: Methotrexate
Methotrexate tablets.

Treatment: Drugs: Bexarotene
Bexarotene tablets.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4) - 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).
Timepoint [1] 0 0
Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)
Secondary outcome [1] 0 0
Percentage of Participants Achieving a CR - 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).
Timepoint [1] 0 0
Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)
Secondary outcome [2] 0 0
Progression-Free Survival (PFS) - 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).
Timepoint [2] 0 0
Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)
Secondary outcome [3] 0 0
Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire - 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.
Timepoint [3] 0 0
Baseline up to End of Treatment (Week 52)
Secondary outcome [4] 0 0
Duration of Response (DOR) - 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).
Timepoint [4] 0 0
Until disease progression, death or data cutoff (Median follow-up 38.8 months)
Secondary outcome [5] 0 0
DOR of Skin Response - 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).
Timepoint [5] 0 0
Until disease progression, death or data cutoff (Median follow-up 38.8 months)
Secondary outcome [6] 0 0
Event-Free Survival (EFS) - 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).
Timepoint [6] 0 0
From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)
Secondary outcome [7] 0 0
Cmax: Maximum Observed Concentration for Brentuximab Vedotin
Timepoint [7] 0 0
Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3
Secondary outcome [8] 0 0
Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin
Timepoint [8] 0 0
Day 1 pre-dose of Cycles 2 and 4
Secondary outcome [9] 0 0
Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin
Timepoint [9] 0 0
Day 1 pre-dose and 30 minutes after infusion ended in Cycles 1 and 3
Secondary outcome [10] 0 0
Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin
Timepoint [10] 0 0
Day 1 pre-dose of Cycles 2 and 4
Secondary outcome [11] 0 0
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin - Blood was collected and evaluated for ATA and neutralizing ATA in all participants who received brentuximab vedotin to assess immunogenicity.
Timepoint [11] 0 0
Baseline up to End of Treatment (Week 52)
Secondary outcome [12] 0 0
Change From Baseline in the Skindex-29 Questionnaire Total Score - 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.
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score - 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.
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - 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.
Timepoint [14] 0 0
First dose of study drug through 30 days after last dose of study drug (Up to 450 days)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
- Concord
Recruitment hospital [2] 0 0
- South Brisbane
Recruitment hospital [3] 0 0
- Adelaide
Recruitment hospital [4] 0 0
- Nedlands
Recruitment hospital [5] 0 0
- East Melbourne
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
- Nedlands
Recruitment postcode(s) [5] 0 0
- East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Austria
State/province [8] 0 0
St. Poelten
Country [9] 0 0
Austria
State/province [9] 0 0
Wien
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
France
State/province [12] 0 0
Nantes Cedex 01
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
France
State/province [14] 0 0
Pessac Cedex
Country [15] 0 0
France
State/province [15] 0 0
Pierre Benite
Country [16] 0 0
France
State/province [16] 0 0
Reims
Country [17] 0 0
Germany
State/province [17] 0 0
Kiel
Country [18] 0 0
Germany
State/province [18] 0 0
Krefeld
Country [19] 0 0
Germany
State/province [19] 0 0
Mainz
Country [20] 0 0
Germany
State/province [20] 0 0
Mannheim
Country [21] 0 0
Germany
State/province [21] 0 0
Minden
Country [22] 0 0
Germany
State/province [22] 0 0
Wurzburg
Country [23] 0 0
Italy
State/province [23] 0 0
Bologna
Country [24] 0 0
Italy
State/province [24] 0 0
Firenze
Country [25] 0 0
Italy
State/province [25] 0 0
Meldola
Country [26] 0 0
Poland
State/province [26] 0 0
Warszawa
Country [27] 0 0
Spain
State/province [27] 0 0
Navarra
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Switzerland
State/province [30] 0 0
Zurich
Country [31] 0 0
United Kingdom
State/province [31] 0 0
West Yorkshire
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Birmingham
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Glasgow
Country [34] 0 0
United Kingdom
State/province [34] 0 0
London
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Millennium Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Seattle Genetics, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01578499
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Millennium Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications