Clinical trial NCT01578499: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Cutaneous Anaplastic Large Cell Lymphoma
Mycosis Fungoides
Cutaneous T-Cell Lymphoma
Keywords: Brentuximab vedotin
ALCANZA
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2012-04-17
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4)
timeFrame: Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)
Secondary outcomes:
measure: Percentage of Participants Achieving a CR
timeFrame: Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)
measure: Progression-Free Survival (PFS)
timeFrame: Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)
measure: Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire
timeFrame: Baseline up to End of Treatment (Week 52)
measure: Duration of Response (DOR)
timeFrame: Until disease progression, death or data cutoff (Median follow-up 38.8 months)
measure: DOR of Skin Response
timeFrame: Until disease progression, death or data cutoff (Median follow-up 38.8 months)
measure: Event-Free Survival (EFS)
timeFrame: From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)
measure: Cmax: Maximum Observed Concentration for Brentuximab Vedotin
timeFrame: Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3
measure: Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin
timeFrame: Day 1 pre-dose of Cycles 2 and 4
measure: Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin
timeFrame: Day 1 pre-dose and 30 minutes after infusion ended in Cycles 1 and 3
measure: Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin
timeFrame: Day 1 pre-dose of Cycles 2 and 4
measure: Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin
timeFrame: Baseline up to End of Treatment (Week 52)
measure: Change From Baseline in the Skindex-29 Questionnaire Total Score
timeFrame: 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)
measure: Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score
timeFrame: 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)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: First dose of study drug through 30 days after last dose of study drug (Up to 450 days)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Hackensack
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Pittsburgh
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Concord
country: Australia
state: New South Wales
city: South Brisbane
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Nedlands
country: Australia
state: Western Australia
city: East Melbourne
country: Australia
city: St. Poelten
country: Austria
city: Wien
country: Austria
city: Leuven
country: Belgium
city: Sao Paulo
country: Brazil
city: Nantes Cedex 01
country: France
city: Paris
country: France
city: Pessac Cedex
country: France
city: Pierre Benite
country: France
city: Reims
country: France
city: Kiel
country: Germany
city: Krefeld
country: Germany
city: Mainz
country: Germany
city: Mannheim
country: Germany
city: Minden
country: Germany
city: Wurzburg
country: Germany
city: Bologna
country: Italy
city: Firenze
country: Italy
city: Meldola
country: Italy
city: Warszawa
country: Poland
city: Pamplona
country: Spain
state: Navarra
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Zurich
country: Switzerland
city: Leeds
country: United Kingdom
state: West Yorkshire
city: Birmingham
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Kim 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.
citation: Valipour 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.
citation: Dummer 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.
citation: Prince 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.