Primary Cutaneous Anaplastic Large Cell LymphomaPhase 3ALCANZANCT01578499
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)
A Phase 3 study testing Brentuximab Vedotin, Methotrexate and Bexarotene in people with Primary Cutaneous Anaplastic Large Cell Lymphoma and Mycosis Fungoides, run by Millennium Pharmaceuticals, Inc. at 41 sites in 12 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Cutaneous Anaplastic Large Cell Lymphoma, Mycosis Fungoides, Cutaneous T-Cell Lymphoma
- What is being tested?
- Brentuximab Vedotin, Methotrexate and Bexarotene
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 41 sitesin 12 countries
- Study dates
- 11 Jun 2012to 6 Jul 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
41 sites in 12 countries.
41 sites in 12 countries
United States8 sites
Study site
Boston, Massachusetts
Study site
Chicago, Illinois
Study site
Hackensack, New Jersey
Study site
Houston, Texas
Study site
Los Angeles, California
Study site
New York, New York
Study site
Palo Alto, California
Study site
Pittsburgh, Pennsylvania
Germany6 sites
Study site
Kiel
Study site
Krefeld
Study site
Mainz
Study site
Mannheim
Study site
Minden
Study site
Würzburg
Australia5 sites
Study site
Adelaide, South Australia
Study site
Concord, New South Wales
Study site
East Melbourne
Study site
Nedlands, Western Australia
Study site
South Brisbane, Queensland
France5 sites
Study site
Nantes
Study site
Paris
Study site
Pessac
Study site
Pierre-Bénite
Study site
Reims
United Kingdom5 sites
Study site
Birmingham
Study site
Glasgow
Study site
Leeds, West Yorkshire
Study site
London
Study site
Manchester
About this study
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
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.
Read the 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.
- Conditions
- Primary Cutaneous Anaplastic Large Cell Lymphoma, Mycosis Fungoides, Cutaneous T-Cell Lymphoma
- Being tested
- Brentuximab Vedotin, Methotrexate, Bexarotene
- Keywords
- Brentuximab vedotin, ALCANZA
- Medical subject headings
- Lymphoma, Primary Cutaneous Anaplastic Large Cell, Mycosis Fungoides, Lymphoma, T-Cell, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brentuximab VedotinDrug
Also called SGN-35
Brentuximab vedotin intravenous injection.
MethotrexateDrug
Methotrexate tablets.
BexaroteneDrug
Bexarotene tablets.
| Study group | Role | What they receive |
|---|---|---|
| Brentuximab vedotin | Experimental | 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). Receives: Drug: Brentuximab Vedotin |
| Methotrexate or Bexarotene | Active comparator | 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. Receives: Drug: Methotrexate; Drug: Bexarotene |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)
Secondary outcomes (14)
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).
Measured: Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)
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).
Measured: Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)
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.
Measured: Baseline up to End of Treatment (Week 52)
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).
Measured: Until disease progression, death or data cutoff (Median follow-up 38.8 months)
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).
Measured: Until disease progression, death or data cutoff (Median follow-up 38.8 months)
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).
Measured: From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)
Cmax: Maximum Observed Concentration for Brentuximab Vedotin
Measured: Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3
Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin
Measured: Day 1 pre-dose of Cycles 2 and 4
Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin
Measured: Day 1 pre-dose and 30 minutes after infusion ended in Cycles 1 and 3
Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin
Measured: Day 1 pre-dose of Cycles 2 and 4
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.
Measured: Baseline up to End of Treatment (Week 52)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: First dose of study drug through 30 days after last dose of study drug (Up to 450 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2012 (estimated)
- Study start11 Jun 2012
- Primary completion31 May 2016
- Study completion6 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Primary Cutaneous Anaplastic Large Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Seagen Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01578499
- Sponsor's protocol ID
- C25001
- Other IDs
- 2010-024215-14
- Acronym
- ALCANZA
- Status last verified
- Dec 2020
- First submitted
- 27 Mar 2012
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Horwitz SM, Scarisbrick JJ, Dummer R, Whittaker S, Duvic M, Kim YH, Quaglino P, Zinzani PL, Bechter O, Eradat H, Pinter-Brown L, Akilov OE, Geskin L, Sanches JA, Ortiz-Romero PL, Weichenthal M, Fisher DC, Walewski J, Trotman J, Taylor K, Dalle S, Stadler R, Lisano J, Bunn V, Little M, Prince HM. Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data. Blood Adv. 2021 Dec 14;5(23):5098-5106. doi: 10.1182/bloodadvances.2021004710.
PubMed 34507350Kim YH, Prince HM, Whittaker S, Horwitz SM, Duvic M, Bechter O, Sanches JA, Stadler R, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Eradat H, Pinter-Brown LC, Ortiz-Romero PL, Akilov OE, Trotman J, Taylor K, Weichenthal M, Walewski J, Fisher D, McNeeley M, Gru AA, Brown L, Palanca-Wessels MC, Lisano J, Onsum M, Bunn V, Little M, Trepicchio WL, Dummer R. Response to brentuximab vedotin versus physician's choice by CD30 expression and large cell transformation status in patients with mycosis fungoides: An ALCANZA sub-analysis. Eur J Cancer. 2021 May;148:411-421. doi: 10.1016/j.ejca.2021.01.054. Epub 2021 Mar 29.
PubMed 33794441Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.
PubMed 32632956Dummer R, Prince HM, Whittaker S, Horwitz SM, Kim YH, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Eradat H, Pinter-Brown L, Sanches JA, Ortiz-Romero PL, Akilov OE, Geskin L, Huen A, Walewski J, Wang Y, Lisano J, Richhariya A, Feliciano J, Zhu Y, Bunn V, Little M, Zagadailov E, Dalal MR, Duvic M. Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study. Eur J Cancer. 2020 Jul;133:120-130. doi: 10.1016/j.ejca.2020.04.010. Epub 2020 Jun 2.
PubMed 32502876Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Sanches JA, Ortiz-Romero PL, Akilov OE, Geskin L, Trotman J, Taylor K, Dalle S, Weichenthal M, Walewski J, Fisher D, Dreno B, Stadler R, Feldman T, Kuzel TM, Wang Y, Palanca-Wessels MC, Zagadailov E, Trepicchio WL, Zhang W, Lin HM, Liu Y, Huebner D, Little M, Whittaker S, Duvic M; ALCANZA study group. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017 Aug 5;390(10094):555-566. doi: 10.1016/S0140-6736(17)31266-7. Epub 2017 Jun 7.
PubMed 28600132
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01578499
- Acronym / sponsor ID
- ALCANZA / C25001
- Conditions
- Primary Cutaneous Anaplastic Large Cell Lymphoma, Mycosis Fungoides, Cutaneous T-Cell Lymphoma
- Keywords
- Brentuximab vedotin, ALCANZA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Seagen Inc.
- Study start
- 11 Jun 2012 (actual)
- Primary completion
- 31 May 2016 (actual)
- Study completion
- 6 Jul 2018 (actual)
- First posted
- 17 Apr 2012 (estimated)
- Results
- Posted 16 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Brentuximab vedotin | Experimental | Drug: Brentuximab VedotinBrentuximab 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 or Bexarotene | Active comparator | Drug: Methotrexate, Drug: BexaroteneMethotrexate 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brentuximab VedotinAlso: SGN-35Brentuximab vedotin intravenous injection. | Drug | Brentuximab vedotin |
| MethotrexateMethotrexate tablets. | Drug | Methotrexate or Bexarotene |
| BexaroteneBexarotene tablets. | Drug | Methotrexate or Bexarotene |
Primary outcome
Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4)
Time frame: 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).
14 secondary outcomes
Percentage of Participants Achieving a CR
Time frame: Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)
Progression-Free Survival (PFS)
Time frame: Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)
Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire
Time frame: Baseline up to End of Treatment (Week 52)
Duration of Response (DOR)
Time frame: Until disease progression, death or data cutoff (Median follow-up 38.8 months)
DOR of Skin Response
Time frame: Until disease progression, death or data cutoff (Median follow-up 38.8 months)
Event-Free Survival (EFS)
Time frame: From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)
Cmax: Maximum Observed Concentration for Brentuximab Vedotin
Time frame: Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3
Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin
Time frame: Day 1 pre-dose of Cycles 2 and 4
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
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
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin
Time frame: Baseline up to End of Treatment (Week 52)
Change From Baseline in the Skindex-29 Questionnaire Total Score
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)
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score
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)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: First dose of study drug through 30 days after last dose of study drug (Up to 450 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34507350Horwitz SM, Scarisbrick JJ, Dummer R, Whittaker S, Duvic M, Kim YH, Quaglino P, Zinzani PL, Bechter O, Eradat H, Pinter-Brown L, Akilov OE, Geskin L, Sanches JA, Ortiz-Romero PL, Weichenthal M, Fisher DC, Walewski J, Trotman J, Taylor K, Dalle S, Stadler R, Lisano J, Bunn V, Little M, Prince HM. Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data. Blood Adv. 2021 Dec 14;5(23):5098-5106. doi: 10.1182/bloodadvances.2021004710.
- Derived from this study: PubMed 33794441Kim YH, Prince HM, Whittaker S, Horwitz SM, Duvic M, Bechter O, Sanches JA, Stadler R, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Eradat H, Pinter-Brown LC, Ortiz-Romero PL, Akilov OE, Trotman J, Taylor K, Weichenthal M, Walewski J, Fisher D, McNeeley M, Gru AA, Brown L, Palanca-Wessels MC, Lisano J, Onsum M, Bunn V, Little M, Trepicchio WL, Dummer R. Response to brentuximab vedotin versus physician's choice by CD30 expression and large cell transformation status in patients with mycosis fungoides: An ALCANZA sub-analysis. Eur J Cancer. 2021 May;148:411-421. doi: 10.1016/j.ejca.2021.01.054. Epub 2021 Mar 29.
- Derived from this study: PubMed 32632956Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.
- Derived from this study: PubMed 32502876Dummer R, Prince HM, Whittaker S, Horwitz SM, Kim YH, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Eradat H, Pinter-Brown L, Sanches JA, Ortiz-Romero PL, Akilov OE, Geskin L, Huen A, Walewski J, Wang Y, Lisano J, Richhariya A, Feliciano J, Zhu Y, Bunn V, Little M, Zagadailov E, Dalal MR, Duvic M. Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study. Eur J Cancer. 2020 Jul;133:120-130. doi: 10.1016/j.ejca.2020.04.010. Epub 2020 Jun 2.
- Derived from this study: PubMed 28600132Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, Zinzani PL, Wolter P, Sanches JA, Ortiz-Romero PL, Akilov OE, Geskin L, Trotman J, Taylor K, Dalle S, Weichenthal M, Walewski J, Fisher D, Dreno B, Stadler R, Feldman T, Kuzel TM, Wang Y, Palanca-Wessels MC, Zagadailov E, Trepicchio WL, Zhang W, Lin HM, Liu Y, Huebner D, Little M, Whittaker S, Duvic M; ALCANZA study group. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017 Aug 5;390(10094):555-566. doi: 10.1016/S0140-6736(17)31266-7. Epub 2017 Jun 7.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Millennium Pharmaceuticals, Inc.
41 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brentuximab Vedotin, Methotrexate and Bexarotene in people with Primary Cutaneous Anaplastic Large Cell Lymphoma and Mycosis Fungoides, run by Millennium Pharmaceuticals, Inc. at 41 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, Germany, Australia, France, United Kingdom and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4) (time frame: Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01578499, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021.