NCT01578499 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2021-01-05

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.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4)

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outcome · POSTED

Percentage of Participants Achieving a CR

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outcome · POSTED

Progression-Free Survival (PFS)

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outcome · POSTED

Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

DOR of Skin Response

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outcome · POSTED

Event-Free Survival (EFS)

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outcome · POSTED

Cmax: Maximum Observed Concentration for Brentuximab Vedotin

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outcome · POSTED

Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin

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outcome · POSTED

Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin

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outcome · POSTED

Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin

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outcome · POSTED

Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin

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outcome · POSTED

Change From Baseline in the Skindex-29 Questionnaire Total Score

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outcome · POSTED

Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score

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outcome · POSTED

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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).
intervention Names
Drug: Brentuximab Vedotin
label
Brentuximab vedotin
type
EXPERIMENTAL
description
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.
intervention Names
Drug: Methotrexate
Drug: Bexarotene
label
Methotrexate or Bexarotene
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Brentuximab vedotin
description
Brentuximab vedotin intravenous injection.
name
Brentuximab Vedotin
other Names
SGN-35
type
DRUG
arm Group Labels
Methotrexate or Bexarotene
description
Methotrexate tablets.
name
Methotrexate
type
DRUG
arm Group Labels
Methotrexate or Bexarotene
description
Bexarotene tablets.
name
Bexarotene
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 131
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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).
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)

secondary Outcomes

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
Percentage of Participants Achieving a CR
time Frame
Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)
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
Progression-Free Survival (PFS)
time Frame
Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)
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
Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire
time Frame
Baseline up to End of Treatment (Week 52)
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
Duration of Response (DOR)
time Frame
Until disease progression, death or data cutoff (Median follow-up 38.8 months)
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 participants without tumors at baseline (MF).
measure
DOR of Skin Response
time Frame
Until disease progression, death or data cutoff (Median follow-up 38.8 months)
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
Event-Free Survival (EFS)
time Frame
From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)
measure
Cmax: Maximum Observed Concentration for Brentuximab Vedotin
time Frame
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
time Frame
Day 1 pre-dose of Cycles 2 and 4
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
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
description
Blood was collected and evaluated for ATA and neutralizing ATA in all participants who received brentuximab vedotin to assess immunogenicity.
measure
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin
time Frame
Baseline up to End of Treatment (Week 52)
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 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)

Full study description

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.

Source references

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.
pmid
34507350
type
DERIVED
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.
pmid
33794441
type
DERIVED
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.
pmid
32632956
type
DERIVED
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.
pmid
32502876
type
DERIVED
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.
pmid
28600132
type
DERIVED