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)

NCT ID: NCT01578499

Last Updated: 2021-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-11
• Study Completion Date: 2018-07-06

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.

Conditions

Primary Cutaneous Anaplastic Large Cell Lymphoma; Mycosis Fungoides; Cutaneous T-Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Brentuximab Vedotin

Intervention Type: DRUG

Brentuximab vedotin intravenous injection.

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.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

Methotrexate tablets.

Bexarotene

Intervention Type: DRUG

Bexarotene tablets.

Interventions

Brentuximab Vedotin

Brentuximab vedotin intravenous injection.

Intervention Type: DRUG

Methotrexate

Methotrexate tablets.

Intervention Type: DRUG

Bexarotene

Bexarotene tablets.

Intervention Type: DRUG

Other Intervention Names

SGN-35

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seagen Inc.

INDUSTRY

Sponsor Role: collaborator

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Los Angeles, California, United States

Palo Alto, California, United States

Chicago, Illinois, United States

Boston, Massachusetts, United States

Hackensack, New Jersey, United States

New York, New York, United States

Pittsburgh, Pennsylvania, United States

Houston, Texas, United States

Concord, New South Wales, Australia

South Brisbane, Queensland, Australia

Adelaide, South Australia, Australia

Nedlands, Western Australia, Australia

East Melbourne, , Australia

Sankt Pölten, , Austria

Vienna, , Austria

Leuven, , Belgium

São Paulo, , Brazil

Nantes, , France

Paris, , France

Pessac, , France

Pierre-Bénite, , France

Reims, , France

Kiel, , Germany

Krefeld, , Germany

Mainz, , Germany

Mannheim, , Germany

Minden, , Germany

Würzburg, , Germany

Bologna, , Italy

Florence, , Italy

Meldola, , Italy

Warsaw, , Poland

Pamplona, Navarre, Spain

Barcelona, , Spain

Madrid, , Spain

Zurich, , Switzerland

Leeds, West Yorkshire, United Kingdom

Birmingham, , United Kingdom

Glasgow, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Brazil; France; Germany; Italy; Poland; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34507350 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33794441 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32632956 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32502876 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28600132 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

https://www.alcanzaclinicaltrial.com/

Related Info

Other Identifiers

2010-024215-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C25001

Identifier Type: -

Identifier Source: org_study_id