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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

Description:

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.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Mycosis Fungoides
Recruiting Status:

Completed

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief 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)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: C25001
  • SECONDARY ID: 2010-024215-14
  • NCT ID: NCT01578499

Conditions

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

Interventions

DrugSynonymsArms
Brentuximab VedotinSGN-35Brentuximab vedotin
MethotrexateMethotrexate or Bexarotene
BexaroteneMethotrexate or Bexarotene

Purpose

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 5 to 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 5 years after enrollment of the last
      participant.
    

Trial Arms

NameTypeDescriptionInterventions
Brentuximab vedotinExperimentalBrentuximab 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).
  • Brentuximab Vedotin
Methotrexate or BexaroteneActive ComparatorMethotrexate 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.
  • Methotrexate
  • Bexarotene

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4)
Time Frame:Each Cycle until disease progression, death or data cutoff (Median overall follow-up 22.9 months)
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Percentage of Participants Achieving a CR
Time Frame:Each Cycle until disease progression, death or data cutoff (Median overall follow-up 22.9 months)
Safety Issue:
Description: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).
Measure:Progression-Free Survival (PFS)
Time Frame:Until disease progression, death or data cutoff (Median PFS follow-up of 17.5 months)
Safety Issue:
Description: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).
Measure:Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire
Time Frame:Baseline up to End of Treatment (Week 52)
Safety Issue:
Description: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.
Measure:Duration of Response (DOR)
Time Frame:Until disease progression, death or data cutoff (Median follow-up 22.9 months)
Safety Issue:
Description: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).
Measure:DOR of Skin Response
Time Frame:Until disease progression, death or data cutoff (Median follow-up 22.9 months)
Safety Issue:
Description: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 patients without tumors at baseline (MF).
Measure:Event-Free Survival (EFS)
Time Frame:From randomization until disease progression, death or data cutoff (Median follow-up 26.1 months)
Safety Issue:
Description: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).
Measure:Cmax: Maximum Observed Concentration for Brentuximab Vedotin
Time Frame:Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3
Safety Issue:
Description:
Measure:Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin
Time Frame:Day 1 pre-dose of Cycles 2 and 4
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin
Time Frame:Baseline up to End of Treatment (Week 52)
Safety Issue:
Description:Blood was collected and evaluated for ATA and neutralizing ATA in all participants who received brentuximab vedotin to assess immunogenicity.
Measure: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 22.9 months)
Safety Issue:
Description: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.
Measure: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 22.9 months)
Safety Issue:
Description: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.
Measure: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 395 days)
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • brentuximab vedotin
  • ALCANZA

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