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)

NCT01578499 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: C250012010-024215-14
• Study Type: interventional
• Target: 131
• Locations: 11 countries
• Sites: 39

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.

Conditions

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

Keywords

Brentuximab vedotin; ALCANZA

Outcome Measures

Primary Outcomes (1)

• 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).

  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

  Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)

• Progression-Free Survival (PFS)

  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

  Baseline up to End of Treatment (Week 52)

• Duration of Response (DOR)

  Until disease progression, death or data cutoff (Median follow-up 38.8 months)

• DOR of Skin Response

  Until disease progression, death or data cutoff (Median follow-up 38.8 months)

Study Arms (2)

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).

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.

Drug: Methotrexate; Drug: Bexarotene

Interventions

Brentuximab Vedotin DRUG

Brentuximab vedotin intravenous injection.

Also known as: SGN-35

Brentuximab vedotin

Methotrexate DRUG

Methotrexate tablets.

Methotrexate or Bexarotene

Bexarotene DRUG

Bexarotene tablets.

Methotrexate or Bexarotene

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead
• Seagen Inc.: collaborator

Study Sites (41)

Unknown Facility

Los Angeles, California, United States

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Palo Alto, California, United States

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Chicago, Illinois, United States

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Boston, Massachusetts, United States

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Hackensack, New Jersey, United States

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New York, New York, United States

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Pittsburgh, Pennsylvania, United States

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Houston, Texas, United States

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Concord, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Adelaide, South Australia, Australia

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Nedlands, Western Australia, Australia

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East Melbourne, Australia

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Sankt Pölten, Austria

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Vienna, Austria

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Leuven, Belgium

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São Paulo, Brazil

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Nantes, France

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Paris, France

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Pessac, France

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Pierre-Bénite, France

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Reims, France

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Kiel, Germany

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Krefeld, Germany

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Mainz, Germany

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Mannheim, Germany

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Minden, Germany

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Würzburg, Germany

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Bologna, Italy

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Florence, Italy

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Meldola, Italy

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Warsaw, Poland

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Pamplona, Navarre, Spain

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Barcelona, Spain

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Madrid, Spain

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Zurich, Switzerland

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Leeds, West Yorkshire, United Kingdom

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Birmingham, United Kingdom

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Glasgow, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Related Publications (5)

• 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.

  PMID: 34507350 DERIVED

• 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.

  PMID: 33794441 DERIVED

• 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.

  PMID: 32632956 DERIVED

• 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.

  PMID: 32502876 DERIVED

• 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.

  PMID: 28600132 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

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

Interventions

Brentuximab Vedotin; Methotrexate; Bexarotene

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

clinicaltrialregistry@tpna.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2012
• First Posted: April 17, 2012
• Study Start: June 11, 2012
• Primary Completion: May 31, 2016
• Study Completion: July 6, 2018
• Last Updated: January 5, 2021
• Results First Posted: March 16, 2018

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

BR (1); IT (3); AU (5); PL (1); US (8); ES (3); CH (1); GB (5); DE (6); FR (5); BE (1)