Cutaneous T-Cell Lymphoma, Mycosis Fungoides, Primary Cutaneous Anaplastic Large Cell Lymphoma
Conditions
Keywords
Brentuximab vedotin, ALCANZA
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.
Interventions
DRUGBrentuximab Vedotin
Brentuximab vedotin intravenous injection.
DRUGMethotrexate
Methotrexate tablets.
DRUGBexarotene
Bexarotene tablets.
Sponsors
Seagen Inc.
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4) | Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months) | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a CR | Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months) | 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). |
| Progression-Free Survival (PFS) | Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months) | 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). |
| Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire | Baseline up to End of Treatment (Week 52) | 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. |
| Duration of Response (DOR) | Until disease progression, death or data cutoff (Median follow-up 38.8 months) | 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). |
| DOR of Skin Response | Until disease progression, death or data cutoff (Median follow-up 38.8 months) | 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). |
| Event-Free Survival (EFS) | From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months) | 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). |
| Cmax: Maximum Observed Concentration for Brentuximab Vedotin | Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3 | — |
| Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin | Day 1 pre-dose of Cycles 2 and 4 | — |
| Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin | Day 1 pre-dose and 30 minutes after infusion ended in Cycles 1 and 3 | — |
| Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin | Day 1 pre-dose of Cycles 2 and 4 | — |
| Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline up to End of Treatment (Week 52) | Blood was collected and evaluated for ATA and neutralizing ATA in all participants who received brentuximab vedotin to assess immunogenicity. |
| Change From Baseline in the Skindex-29 Questionnaire Total Score | 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) | 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. |
| Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | 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) | 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. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | First dose of study drug through 30 days after last dose of study drug (Up to 450 days) | 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. |
Countries
Australia, Austria, Belgium, Brazil, France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 34 investigative sites in Australia, Belgium, Brazil, France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom, United States from 11 June 2012 to the Primary Completion data of 06 July 2018.
Pre-assignment details
Participants with a diagnosis of cluster of differentiation antigen 30 (CD30)-Positive Cutaneous T-Cell Lymphoma were enrolled equally in 1 of 2 arms: brentuximab vedotin 1.8 mg/kg or physician's choice (Methotrexate or Bexarotene).
Participants by arm
| Arm | Count |
|---|---|
| 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). | 66 |
| 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. | 64 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 20 | 25 |
| Overall Study | Died and End of Study Page not Completed | 2 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Reason not Specified | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 16 |
Baseline characteristics
| Characteristic | Methotrexate or Bexarotene | Total | Brentuximab Vedotin |
|---|---|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 14.43 | 58.0 years STANDARD_DEVIATION 14.12 | 59.4 years STANDARD_DEVIATION 13.8 |
| Race/Ethnicity, Customized Asian | 5 participants | 6 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 6 participants | 3 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 6 participants | 8 participants | 2 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 50 participants | 110 participants | 60 participants |
| Race/Ethnicity, Customized Not reported | 1 participants | 4 participants | 3 participants |
| Race/Ethnicity, Customized Other | 2 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized White | 53 participants | 109 participants | 56 participants |
| Region of Enrollment Australia | 8 Participants | 20 Participants | 12 Participants |
| Region of Enrollment Belgium | 2 Participants | 6 Participants | 4 Participants |
| Region of Enrollment Brazil | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment France | 3 Participants | 7 Participants | 4 Participants |
| Region of Enrollment Germany | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Italy | 6 Participants | 18 Participants | 12 Participants |
| Region of Enrollment Poland | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Spain | 3 Participants | 5 Participants | 2 Participants |
| Region of Enrollment Switzerland | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment United Kingdom | 15 Participants | 23 Participants | 8 Participants |
| Region of Enrollment United States | 17 Participants | 31 Participants | 14 Participants |
| Sex: Female, Male Female | 28 Participants | 61 Participants | 33 Participants |
| Sex: Female, Male Male | 34 Participants | 67 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 66 | 25 / 62 |
| other Total, other adverse events | 60 / 66 | 51 / 62 |
| serious Total, serious adverse events | 18 / 66 | 18 / 62 |
Outcome results
Primary
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).
Time frame: Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin | Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4) | 54.7 percentage of participants |
| Methotrexate or Bexarotene | Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4) | 12.5 percentage of participants |
Comparison: Based on a two-sided Χ² test with a significance level of 0.05, and a 10% dropout rate, a sample size of approximately 124 participants was calculated to provide 90% power to detect a 30% improvement in ORR4 in the brentuximab vedotin group.p-value: <0.00195% CI: [27.5, 56.8]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score
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.
Time frame: 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)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 12 | 7.94 score on a scale | Standard Deviation 18.837 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 6-9 months LTFU | -0.19 score on a scale | Standard Deviation 19.648 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 8 | 5.96 score on a scale | Standard Deviation 16.03 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 9-12 months LTFU | 3.62 score on a scale | Standard Deviation 17.651 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 14 | 9.04 score on a scale | Standard Deviation 14.104 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 12-15 months LTFU | 8.33 score on a scale | Standard Deviation 14.918 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 6 | 4.23 score on a scale | Standard Deviation 14.257 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 15-18 months LTFU | 3.03 score on a scale | Standard Deviation 12.618 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 16 | 5.08 score on a scale | Standard Deviation 9.23 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 18-21 months LTFU | 3.35 score on a scale | Standard Deviation 11.117 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 10 | 6.61 score on a scale | Standard Deviation 16.971 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 21-24 months LTFU | 1.51 score on a scale | Standard Deviation 5.471 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at End of Treatment | 0.35 score on a scale | Standard Deviation 16.067 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 24-27 months LTFU | 4.20 score on a scale | Standard Deviation 7.952 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 4 | 1.75 score on a scale | Standard Deviation 12.014 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 27-30 months LTFU | -1.57 score on a scale | Standard Deviation 17.488 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 3-6 months LTFU | 16.00 score on a scale | Standard Deviation 18.385 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at >30 months LTFU | -6.22 score on a scale | Standard Deviation 15.222 |
| Brentuximab Vedotin | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 2 | 1.43 score on a scale | Standard Deviation 10.168 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at >30 months LTFU | -2.85 score on a scale | Standard Deviation 5.518 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 2 | -0.37 score on a scale | Standard Deviation 11.723 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 4 | 1.78 score on a scale | Standard Deviation 10.74 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 6 | 2.24 score on a scale | Standard Deviation 13.108 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 8 | 2.54 score on a scale | Standard Deviation 10.809 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 10 | 4.38 score on a scale | Standard Deviation 15.04 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 12 | 8.61 score on a scale | Standard Deviation 21.024 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 14 | 10.75 score on a scale | Standard Deviation 13.615 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at Cycle 16 | 7.88 score on a scale | Standard Deviation 23.432 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at End of Treatment | -2.29 score on a scale | Standard Deviation 17.171 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 3-6 months LTFU | -2.92 score on a scale | Standard Deviation 8.367 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 6-9 months LTFU | -2.59 score on a scale | Standard Deviation 12.473 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 9-12 months LTFU | -5.32 score on a scale | Standard Deviation 10.555 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 12-15 months LTFU | -1.34 score on a scale | Standard Deviation 11.905 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 15-18 months LTFU | 2.94 score on a scale | Standard Deviation 14.756 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 18-21 months LTFU | -0.19 score on a scale | Standard Deviation 14.316 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 21-24 months LTFU | 0.61 score on a scale | Standard Deviation 14.505 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 24-27 months LTFU | 1.42 score on a scale | Standard Deviation 17.87 |
| Methotrexate or Bexarotene | Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score | Change at 27-30 months LTFU | 1.93 score on a scale | Standard Deviation 8.716 |
Secondary
Change From Baseline in the Skindex-29 Questionnaire Total Score
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.
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)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 12 | -23.37 score on a scale | Standard Deviation 21.555 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 6-9 months LTFU | -8.04 score on a scale | Standard Deviation 8.8 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 8 | -21.73 score on a scale | Standard Deviation 18.882 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 9-12 months LTFU | -7.94 score on a scale | Standard Deviation 15.582 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 14 | -19.72 score on a scale | Standard Deviation 20.98 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 12-15 months LTFU | -16.21 score on a scale | Standard Deviation 18.438 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 6 | -17.59 score on a scale | Standard Deviation 17.77 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 15-18 months LTFU | -19.18 score on a scale | Standard Deviation 19.475 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 16 | -19.35 score on a scale | Standard Deviation 18.911 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 18-21 months LTFU | -19.27 score on a scale | Standard Deviation 20.962 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 10 | -22.47 score on a scale | Standard Deviation 21.722 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 21-24 months LTFU | -16.60 score on a scale | Standard Deviation 19.875 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at End of Treatment | -16.26 score on a scale | Standard Deviation 23.281 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 24-27 months LTFU | -17.04 score on a scale | Standard Deviation 15.982 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 4 | -14.60 score on a scale | Standard Deviation 17.488 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 27-30 months LTFU | -12.45 score on a scale | Standard Deviation 19.639 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at >30 months LTFU | -11.49 score on a scale | Standard Deviation 22.47 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 3-6 months LTFU | -1.07 score on a scale | Standard Deviation 3.704 |
| Brentuximab Vedotin | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 2 | -5.44 score on a scale | Standard Deviation 11.055 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 27-30 months LTFU | -7.97 score on a scale | Standard Deviation 16.401 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 2 | -2.49 score on a scale | Standard Deviation 11.959 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 4 | -6.71 score on a scale | Standard Deviation 9.755 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 6 | -5.40 score on a scale | Standard Deviation 9.758 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 8 | -7.28 score on a scale | Standard Deviation 16.769 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 10 | -3.71 score on a scale | Standard Deviation 21.752 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 12 | -5.22 score on a scale | Standard Deviation 17.704 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 14 | -7.49 score on a scale | Standard Deviation 22.463 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at Cycle 16 | 0.75 score on a scale | Standard Deviation 10.308 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at End of Treatment | -0.96 score on a scale | Standard Deviation 18.973 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 3-6 months LTFU | -9.48 score on a scale | Standard Deviation 21.629 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 6-9 months LTFU | -9.68 score on a scale | Standard Deviation 17.789 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 9-12 months LTFU | -4.93 score on a scale | Standard Deviation 14.516 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 12-15 months LTFU | -11.16 score on a scale | Standard Deviation 18.183 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 15-18 months LTFU | -8.53 score on a scale | Standard Deviation 12.768 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 18-21 months LTFU | -5.46 score on a scale | Standard Deviation 16.679 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 21-24 months LTFU | -6.86 score on a scale | Standard Deviation 14.991 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at 24-27 months LTFU | -9.05 score on a scale | Standard Deviation 23.99 |
| Methotrexate or Bexarotene | Change From Baseline in the Skindex-29 Questionnaire Total Score | Change at >30 months LTFU | -1.07 score on a scale | Standard Deviation 18.886 |
Secondary
Cmax: Maximum Observed Concentration for Brentuximab Vedotin
Time frame: Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3
Population: The pharmacokinetic (PK) population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin | Cmax: Maximum Observed Concentration for Brentuximab Vedotin | Cycle 1 Day 1 | 38.36 ug/mL | Standard Deviation 9.427 |
| Brentuximab Vedotin | Cmax: Maximum Observed Concentration for Brentuximab Vedotin | Cycle 3 Day 1 | 40.14 ug/mL | Standard Deviation 12.697 |
| Methotrexate or Bexarotene | Cmax: Maximum Observed Concentration for Brentuximab Vedotin | Cycle 1 Day 1 | 38.40 ug/mL | Standard Deviation 8.912 |
| Methotrexate or Bexarotene | Cmax: Maximum Observed Concentration for Brentuximab Vedotin | Cycle 3 Day 1 | 36.69 ug/mL | Standard Deviation 14.249 |
Secondary
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
Population: The PK population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin | Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin | Cycle 1 Day 1 | 2.53 ng/mL | Standard Deviation 1.382 |
| Brentuximab Vedotin | Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin | Cycle 3 Day 1 | 2.96 ng/mL | Standard Deviation 1.176 |
| Methotrexate or Bexarotene | Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin | Cycle 1 Day 1 | 3.34 ng/mL | Standard Deviation 1.901 |
| Methotrexate or Bexarotene | Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin | Cycle 3 Day 1 | 3.08 ng/mL | Standard Deviation 1.276 |
Secondary
Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin
Time frame: Day 1 pre-dose of Cycles 2 and 4
Population: The PK population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin | Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin | Cycle 2 Day 1 | 3.57 ug/mL | Standard Deviation 10.101 |
| Brentuximab Vedotin | Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin | Cycle 4 Day 1 | 0.99 ug/mL | Standard Deviation 0.528 |
| Methotrexate or Bexarotene | Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin | Cycle 2 Day 1 | 0.58 ug/mL | Standard Deviation 0.517 |
| Methotrexate or Bexarotene | Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin | Cycle 4 Day 1 | 0.78 ug/mL | Standard Deviation 0.446 |
Secondary
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
Population: The PK population included participants with sufficient dose and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. Here 'Number analyzed' is the number of participants with evaluable data at the specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin | Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin | Cycle 2 Day 1 | 0.11 ng/mL | Standard Deviation 0.095 |
| Brentuximab Vedotin | Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin | Cycle 4 Day 1 | 0.14 ng/mL | Standard Deviation 0.113 |
| Methotrexate or Bexarotene | Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin | Cycle 2 Day 1 | 0.09 ng/mL | Standard Deviation 0.06 |
| Methotrexate or Bexarotene | Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin | Cycle 4 Day 1 | 0.11 ng/mL | Standard Deviation 0.091 |
Secondary
DOR of Skin Response
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).
Time frame: Until disease progression, death or data cutoff (Median follow-up 38.8 months)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Skin responders in ITT population were analyzed in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | DOR of Skin Response | 18.9 months |
| Methotrexate or Bexarotene | DOR of Skin Response | 18.3 months |
Secondary
Duration of Response (DOR)
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).
Time frame: Until disease progression, death or data cutoff (Median follow-up 38.8 months)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Responders in ITT population were analyzed in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | Duration of Response (DOR) | 15.1 months |
| Methotrexate or Bexarotene | Duration of Response (DOR) | 18.4 months |
Secondary
Event-Free Survival (EFS)
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).
Time frame: From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | Event-Free Survival (EFS) | 9.4 months |
| Methotrexate or Bexarotene | Event-Free Survival (EFS) | 2.3 months |
Secondary
Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire
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.
Time frame: Baseline up to End of Treatment (Week 52)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment. Here number of participants analyzed are participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brentuximab Vedotin | Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire | -28.08 score on a scale | Standard Deviation 26.863 |
| Methotrexate or Bexarotene | Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire | -8.62 score on a scale | Standard Deviation 17.013 |
Comparison: P-value is calculated using the analysis of covariance (ANCOVA) model controlling for baseline symptom domain score, eastern cooperative oncology group (ECOG) performance status score (=0 and ≥1), and disease diagnosis (pcALCL and MF) between the brentuximab vedotin and comparator (methotrexate or bexarotene) arms.p-value: <0.00195% CI: [-26.7, -11.4]ANCOVA
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: First dose of study drug through 30 days after last dose of study drug (Up to 450 days)
Population: The Safety population included participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brentuximab Vedotin | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 63 participants |
| Brentuximab Vedotin | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 18 participants |
| Methotrexate or Bexarotene | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 56 participants |
| Methotrexate or Bexarotene | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 18 participants |
Secondary
Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin
Blood was collected and evaluated for ATA and neutralizing ATA in all participants who received brentuximab vedotin to assess immunogenicity.
Time frame: Baseline up to End of Treatment (Week 52)
Population: The Safety population included participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: Transiently Positive | 4 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: ATA Negative | 0 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: ATA positive | 6 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: ATA Positive | 0 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: Persistently Positive | 2 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: Transiently Positive | 0 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: ATA negative | 8 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: Persistently Positive | 0 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: Neutralizing ATA Positive | 4 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: Neutralizing ATA Positive | 0 participants |
| Brentuximab Vedotin | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Immunogenicity-evaluable participants | 14 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: Neutralizing ATA Positive | 2 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Immunogenicity-evaluable participants | 46 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: ATA negative | 23 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: ATA positive | 19 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: Transiently Positive | 9 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: Persistently Positive | 10 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Negative: Neutralizing ATA Positive | 14 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: ATA Negative | 1 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: ATA Positive | 3 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: Transiently Positive | 3 participants |
| Methotrexate or Bexarotene | Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin | Baseline Positive: Persistently Positive | 0 participants |
Secondary
Percentage of Participants Achieving a CR
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).
Time frame: Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin | Percentage of Participants Achieving a CR | 17.2 percentage of participants |
| Methotrexate or Bexarotene | Percentage of Participants Achieving a CR | 1.6 percentage of participants |
p-value: 0.000295% CI: [-2.5, 33]Cochran-Mantel-Haenszel
Secondary
Progression-Free Survival (PFS)
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).
Time frame: Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months)
Population: The ITT population included all participants who were identified as CD30+ by the Ventana anti-CD30 (Ber-H2) assay and were randomized to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin | Progression-Free Survival (PFS) | 16.7 months |
| Methotrexate or Bexarotene | Progression-Free Survival (PFS) | 3.5 months |
p-value: <0.00195% CI: [0.247, 0.577]Log Rank