Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory (r/r) Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma

Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01492088
Collaborator
(none)
36
Enrollment
18
Locations
2
Arms
71.9
Actual Duration (Months)
2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and pharmacokinetics, and determine the pediatric maximum tolerated dose and/or or recommended phase 2 dose of brentuximab vedotin.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Brentuximab vedotin
Phase 1/Phase 2

Detailed Description

The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat children who have relapsed or refractory (r/r) anaplastic large-cell lymphoma (sALCL) or Hodgkin lymphoma (HL). This study will look at the maximum tolerated dose and/or recommended phase 2 dose, safety and pharmacokinetics of brentuximab vedotin along with overall response of people who took brentuximab vedotin.

The study enrolled 36 patients. In the phase 1 portion of the study, 12 participants were enrolled to receive brentuximab vedotin 1.4-1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.

Once the maximum tolerated dose and/or recommended phase 2 dose and pharmacokinetics of brentuximab vedotin was reached, participants were enrolled by diagnosis into two phase 2 study arms: relapsed or refractory sALCL or relapsed or refractory HL and received brentuximab vedotin 1.8 mg/kg as 30-minute IV on Day 1 of every 21-day cycle for up to 16 cycles. One participant received a maximum of 20 cycles at the joint discretion of the sponsor and the investigator for continued clinical benefit.

This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 5 years. Participants made multiple visits to the clinic, and were contacted by telephone every 12 weeks for 12 months after the end of treatment (EOT) for progression free survival and then every 6 months until death, study closure, or 2 years after enrollment of the last participant for overall survival.

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of Brentuximab Vedotin (SGN-35) in Pediatric Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
Actual Study Start Date :
Apr 16, 2012
Actual Primary Completion Date :
Oct 12, 2016
Actual Study Completion Date :
Apr 12, 2018

Arms and Interventions

ArmIntervention/Treatment
Experimental: Brentuximab vedotin: Phase 1

Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. Dose was escalated up to 1.8 mg/kg using a 3 + 3 dose escalation design to determine a maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) depending upon the dose limiting toxicity (DLT).

Drug: Brentuximab vedotin
Brentuximab vedotin IV infusion
Other Names:
  • SGN-35
  • ADCETRIS
  • Experimental: Brentuximab vedotin: Phase 2

    Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there is evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.

    Drug: Brentuximab vedotin
    Brentuximab vedotin IV infusion
    Other Names:
  • SGN-35
  • ADCETRIS
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]

      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 Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

    2. Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]

      Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.

    3. Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]

      Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.

    4. Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]

      Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.

    5. Serum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]

      Blood samples were collected and tested for conjugated and unconjugated antibodies.

    6. Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]

      Blood samples were collected and tested for MMAE plasma concentrations.

    7. Overall Response Rate (ORR) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months)]

      Overall response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.

    Secondary Outcome Measures

    1. Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) [Baseline up to EOT (Up to 15 months)]

      Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA and nATA development) using a laboratory test. ATA-positive samples were further characterized as transiently ATA positive (defined as 1 or 2 post-Baseline ATA-positive responses), persistently ATA positive (defined as more than 2 post-Baseline ATA positive responses), and nATA positive or negative.

    2. Overall Response Rate (ORR) (Phase 1) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)]

      Overall response rate is defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.

    3. Time to Progression (TTP) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)]

      TTP is defined as the time in months from first dose until the first subsequent documentation of objective tumor progression. Progressive disease (PD) is defined as any new lesion or increase by ≥50% of previously involved sites from nadir.

    4. Time to Response (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)]

      Time to response is defined as the time in months from the first dose of study treatment until the date of the first assessment of confirmed CR or PR. as assessed by an IRF using IWG revised response criteria for malignant lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.

    5. Duration of Response (DOR) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)]

      DOR is defined as the time in months from the date of first documentation of a CR or PR to the date of first documentation of tumor progression or PD per IRF assessment according to IWG criteria or to death due to any cause, whichever comes first. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.

    6. Event Free Survival (EFS) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)]

      EFS is defined as the time in months from first dose until any cause of treatment failure: disease progression, premature discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.

    7. Progression Free Survival (PFS) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)]

      PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.

    8. Overall Survival (OS) (Phase 1 and 2) [Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrolment of the last participant (Up to 72 months)]

      OS is the time in months from start of study treatment to date of death due to any cause.

    9. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) [From the first dose through 30 days after the last dose of study medication (up to 15 months)]

      An 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 experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

    10. Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]

      Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.

    11. Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]

      Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.

    12. Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]

      Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.

    13. Serum Concentration of Total Antibodies (Conjugated and Unconjugated) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]

      Blood samples were collected and tested for conjugated and unconjugated antibodies.

    14. Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]

      Blood samples were collected and tested for MMAE plasma concentrations.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male or female participants aged 2 to <18 years (5 to <18 years for Hodgkin lymphoma [HL])

    • Diagnosis of systemic anaplastic large-cell lymphoma (sALCL), or HL for which standard, curative, life-prolonging, or palliative treatment does not exist or is no longer effective

    • Participants with sALCL must have documented anaplastic lymphoma kinase (ALK) status and must be beyond first remission or refractory to front-line chemotherapy

    • Participants diagnosed with any relapsed or refractory CD30+ hematologic malignancy (e.g., primary mediastinal B-cell lymphoma) may be included in phase 1 of the study

    • Participants with HL must be in their second of later relapse, have failed systemic chemotherapy either as induction therapy for advanced stage disease or salvage therapy, and were ineligible for, refused, or previously received a stem cell transplant

    • Performance score ≥ 60 from Lansky Play Performance Scale if ≤16 years

    • Negative pregnancy test

    • Fertile Participants must use 2 effective methods of contraception prior to and through 6 months after the last dose of the study drug

    Exclusion Criteria:
    • Current diagnosis of primary cutaneous ALCL (those with systemic ALCL are eligible)

    • Received an allogeneic stem cell transplant <3 months prior to the first dose of study medication, or presence of polymerase chain reaction (PCR)-detectable cytomegalovirus (CMV) in any post-allogeneic transplant participant

    • Receiving immunosuppressive therapy

    • Receiving systemic therapy for chronic graft-versus-host disease (topical therapy is allowed)

    • Previous treatment with any anti-CD30 antibody

    • Therapeutic monoclonal antibody use within the longer of 6 weeks or 5 plasma half-lives

    • Systemic cardiac disease that would, in the opinion of the investigator or medical monitor, interfere with assessment of efficacy or safety of the drug

    • History of another primary malignancy not in remission for at least 3 years (the following are exempt from the 3-year limit: nonmelanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)

    • Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML

    • History of cirrhosis

    • Active systemic viral, bacterial, or fungal infection requiring antimicrobial, antiviral therapy or antifungal therapy within 2 weeks prior to the first dose of study drug (routine antimicrobial prophylaxis is acceptable)

    • Concurrent therapy with other anti-neoplastic or experimental agents

    • Systemic corticosteroid therapy <7 days prior to first dose of the study medication

    • Any serious underlying medical condition that, in the opinion of the investigator or medical monitor, would impair their ability to receive or tolerate the planned treatment

    • Known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation

    • Received nitrogen mustard agents, melphalan, or BCNU therapy within 6 weeks prior to the first study dose

    • Prior autologous hematopoietic stem cell infusion <4 weeks prior to first study dose

    • Grade 2 or greater unresolved toxicity from prior antineoplastic therapy

    • Grade 2 or greater peripheral neuropathy

    • Female participants who are both lactating and breastfeeding, or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug

    • Received local palliative radiation therapy <14 days prior to the first dose of study medication

    • Received radiation therapy to more than 25% of the bone marrow-containing spaces < 84 days prior to first dose of study medication

    • Received a strong or listed moderate inhibitor of CYP3A4 <2 weeks prior to first study dose

    • Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1AuroraColoradoUnited States
    2Kansas CityMissouriUnited States
    3New YorkNew YorkUnited States
    4HoustonTexasUnited States
    5Bordeaux CedexFrance
    6LyonFrance
    7Paris Cedex 12France
    8BerlinGermany
    9FrankfurtGermany
    10GiessenGermany
    11HalleGermany
    12MunsterGermany
    13PadovaItaly
    14RomaItaly
    15Mexico DfMexico
    16RotterdamNetherlands
    17BarcelonaSpain
    18LondonUnited Kingdom

    Sponsors and Collaborators

    • Millennium Pharmaceuticals, Inc.

    Investigators

    • Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Millennium Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT01492088
    Other Study ID Numbers:
    • C25002
    • 2011-001240-29
    • U1111-1158-2613
    • 133300410A0384
    • NL38209.078.11
    First Posted:
    Dec 14, 2011
    Last Update Posted:
    Nov 20, 2018
    Last Verified:
    Nov 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Millennium Pharmaceuticals, Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants took part in the study at 12 investigative sites in United States, France, Germany, Netherlands, United Kingdom, Italy, Spain and Mexico from 16-April-2012 to 12-April-2018.
    Pre-assignment DetailParticipants with diagnosis of relapsed or refractory (r/r) sALCL/HL were enrolled to receive brentuximab vedotin 1.4-1.8 mg/kg, intravenous infusion on Day 1 of every 21-day cycle for up to 16 cycles. Treatment beyond 16 cycles was permitted at joint discretion of sponsor and investigator for participants experiencing continued clinical benefit.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Period Title: Overall Study
    STARTED31617
    COMPLETED023
    NOT COMPLETED31414

    Baseline Characteristics

    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Total of all reporting groups
    Overall Participants3161736
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    14.7
    (1.15)
    14.5
    (2.68)
    11.5
    (3.18)
    13.1
    (3.19)
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    7
    43.8%
    3
    17.6%
    11
    30.6%
    Male
    2
    66.7%
    9
    56.3%
    14
    82.4%
    25
    69.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    4
    23.5%
    4
    11.1%
    Not Hispanic or Latino
    3
    100%
    14
    87.5%
    12
    70.6%
    29
    80.6%
    Unknown or Not Reported
    0
    0%
    2
    12.5%
    1
    5.9%
    3
    8.3%
    Race/Ethnicity, Customized (Count of Participants)
    White
    2
    66.7%
    13
    81.3%
    16
    94.1%
    31
    86.1%
    Asian
    1
    33.3%
    0
    0%
    1
    5.9%
    2
    5.6%
    Other
    0
    0%
    2
    12.5%
    0
    0%
    2
    5.6%
    Not Reported
    0
    0%
    1
    6.3%
    0
    0%
    1
    2.8%
    Region of Enrollment (Count of Participants)
    United States
    2
    66.7%
    1
    6.3%
    1
    5.9%
    4
    11.1%
    France
    0
    0%
    2
    12.5%
    0
    0%
    2
    5.6%
    Germany
    0
    0%
    4
    25%
    1
    5.9%
    5
    13.9%
    Netherlands
    0
    0%
    1
    6.3%
    2
    11.8%
    3
    8.3%
    United Kingdom
    0
    0%
    1
    6.3%
    2
    11.8%
    3
    8.3%
    Italy
    1
    33.3%
    7
    43.8%
    6
    35.3%
    14
    38.9%
    Spain
    0
    0%
    0
    0%
    4
    23.5%
    4
    11.1%
    Mexico
    0
    0%
    0
    0%
    1
    5.9%
    1
    2.8%
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    167.17
    (10.865)
    165.31
    (14.350)
    149.54
    (17.783)
    158.02
    (17.493)
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    53.10
    (9.924)
    57.85
    (17.539)
    42.16
    (15.162)
    50.04
    (17.361)
    Body Surface Area (m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [m^2]
    1.562
    (0.0967)
    1.617
    (0.2938)
    1.313
    (0.3103)
    1.469
    (0.3228)

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1)
    DescriptionAn 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 Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
    Time FrameFrom the first dose through 30 days after the last dose of study medication (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants39
    TEAE
    3
    100%
    9
    56.3%
    SAE
    0
    0%
    4
    25%
    2. Primary Outcome
    TitleNumber of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1)
    DescriptionAbnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
    Time FrameFrom the first dose through 30 days after the last dose of study medication (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants39
    Gamma-glutamyltransferase increased
    0
    0%
    1
    6.3%
    Transaminases increased
    0
    0%
    1
    6.3%
    Lymphocyte count decreased
    1
    33.3%
    1
    6.3%
    Neutrophil count decreased
    0
    0%
    1
    6.3%
    Blood bicarbonate decreased
    0
    0%
    1
    6.3%
    Weight decreased
    0
    0%
    1
    6.3%
    Hypocalaemia
    0
    0%
    2
    12.5%
    Hyperuricaemia
    0
    0%
    1
    6.3%
    3. Primary Outcome
    TitleNumber of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1)
    DescriptionVital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.
    Time FrameFrom the first dose through 30 days after the last dose of study medication (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants39
    Count of Participants [Participants]
    0
    0%
    0
    0%
    4. Primary Outcome
    TitleAntibody-drug Conjugate (ADC) Serum Concentrations (Phase 1)
    DescriptionBlood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
    Time FrameCycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

    Outcome Measure Data

    Analysis Population Description
    Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 19.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants00
    5. Primary Outcome
    TitleSerum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1)
    DescriptionBlood samples were collected and tested for conjugated and unconjugated antibodies.
    Time FrameCycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

    Outcome Measure Data

    Analysis Population Description
    Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 20.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants00
    6. Primary Outcome
    TitleMonomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1)
    DescriptionBlood samples were collected and tested for MMAE plasma concentrations.
    Time FrameCycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

    Outcome Measure Data

    Analysis Population Description
    Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 21.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants00
    7. Primary Outcome
    TitleOverall Response Rate (ORR) (Phase 1 and 2)
    DescriptionOverall response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
    Time FrameCycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r Hodgkin Lymphoma (HL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31517
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    47
    293.8%
    53
    311.8%
    8. Secondary Outcome
    TitleNumber of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2)
    DescriptionBlood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA and nATA development) using a laboratory test. ATA-positive samples were further characterized as transiently ATA positive (defined as 1 or 2 post-Baseline ATA-positive responses), persistently ATA positive (defined as more than 2 post-Baseline ATA positive responses), and nATA positive or negative.
    Time FrameBaseline up to EOT (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Participants from the Safety Population, all enrolled participants who received at least one dose of brentuximab vedotin, with data available for analysis.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31617
    ATA status: Transiently positive
    1
    33.3%
    4
    25%
    7
    41.2%
    ATA status: Persistently positive
    0
    0%
    2
    12.5%
    0
    0%
    nATA status: Positive
    0
    0%
    5
    31.3%
    4
    23.5%
    9. Secondary Outcome
    TitleOverall Response Rate (ORR) (Phase 1)
    DescriptionOverall response rate is defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
    Time FrameCycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Participants enrolled in Phase 1 of the study were evaluated for this outcome measure.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants38
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    63
    393.8%
    10. Secondary Outcome
    TitleTime to Progression (TTP) (Phase 1 and 2)
    DescriptionTTP is defined as the time in months from first dose until the first subsequent documentation of objective tumor progression. Progressive disease (PD) is defined as any new lesion or increase by ≥50% of previously involved sites from nadir.
    Time FrameCycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. TTP was censored on last radiological assessment of measured lesions documenting absence of PD for participants who did not have tumor progression.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31617
    Median (95% Confidence Interval) [months]
    2.7
    4.8
    6.2
    11. Secondary Outcome
    TitleTime to Response (Phase 1 and 2)
    DescriptionTime to response is defined as the time in months from the first dose of study treatment until the date of the first assessment of confirmed CR or PR. as assessed by an IRF using IWG revised response criteria for malignant lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
    Time FrameCycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Time to response was censored on the last radiological assessment of measured lesions documenting absence of CR or PR for participants who did not have CR or PR.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31517
    Median (95% Confidence Interval) [months]
    NA
    2.7
    1.5
    12. Secondary Outcome
    TitleDuration of Response (DOR) (Phase 1 and 2)
    DescriptionDOR is defined as the time in months from the date of first documentation of a CR or PR to the date of first documentation of tumor progression or PD per IRF assessment according to IWG criteria or to death due to any cause, whichever comes first. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
    Time FrameCycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)

    Outcome Measure Data

    Analysis Population Description
    Participants with response from the Safety Population, all enrolled participants who received at least one dose of brentuximab vedotin, with data available for analysis. Duration of response was censored at last observation documenting absence of PD for participants who did not have tumor progression.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants079
    Median (95% Confidence Interval) [months]
    NA
    30.3
    13. Secondary Outcome
    TitleEvent Free Survival (EFS) (Phase 1 and 2)
    DescriptionEFS is defined as the time in months from first dose until any cause of treatment failure: disease progression, premature discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
    Time FrameCycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. EFS was censored on the last follow-up date if none of the above events occur during the study.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31617
    Median (95% Confidence Interval) [months]
    2.7
    2.1
    4.8
    14. Secondary Outcome
    TitleProgression Free Survival (PFS) (Phase 1 and 2)
    DescriptionPFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
    Time FrameCycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. PFS was censored on the day following the date of last radiological assessment of measured lesions documenting absence of PD for participants who did not have tumor progression.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31617
    Median (95% Confidence Interval) [months]
    2.7
    3.8
    6.2
    15. Secondary Outcome
    TitleOverall Survival (OS) (Phase 1 and 2)
    DescriptionOS is the time in months from start of study treatment to date of death due to any cause.
    Time FrameEvery 6 months after EOT, until the sooner of death, study closure, or 2 years after enrolment of the last participant (Up to 72 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31617
    Median (95% Confidence Interval) [months]
    NA
    NA
    NA
    16. Secondary Outcome
    TitleNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2)
    DescriptionAn 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 experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
    Time FrameFrom the first dose through 30 days after the last dose of study medication (up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31617
    TEAEs
    3
    100%
    16
    100%
    17
    100%
    SAEs
    0
    0%
    7
    43.8%
    1
    5.9%
    17. Secondary Outcome
    TitleNumber of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2)
    DescriptionAbnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
    Time FrameFrom the first dose through 30 days after the last dose of study medication (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31617
    Gamma-glutamyltransferase increased
    0
    0%
    2
    12.5%
    0
    0%
    Alanine aminotransferase increased
    0
    0%
    1
    6.3%
    0
    0%
    Aspartate aminotransferase increased
    0
    0%
    1
    6.3%
    0
    0%
    Transaminases increased
    0
    0%
    1
    6.3%
    0
    0%
    Lymphocyte count decreased
    1
    33.3%
    0
    0%
    2
    11.8%
    Neutrophil count decreased
    0
    0%
    0
    0%
    2
    11.8%
    White blood cell count decreased
    0
    0%
    0
    0%
    1
    5.9%
    Blood bicarbonate decreased
    0
    0%
    1
    6.3%
    0
    0%
    Weight decreased
    0
    0%
    0
    0%
    1
    5.9%
    C-reactive protein increased
    0
    0%
    1
    6.3%
    0
    0%
    Blood alkaline phosphatase increased
    0
    0%
    1
    6.3%
    0
    0%
    18. Secondary Outcome
    TitleNumber of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2)
    DescriptionVital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.
    Time FrameFrom the first dose through 30 days after the last dose of study medication (Up to 15 months)

    Outcome Measure Data

    Analysis Population Description
    Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants31617
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    19. Secondary Outcome
    TitleAntibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2)
    DescriptionBlood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
    Time FrameCycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

    Outcome Measure Data

    Analysis Population Description
    PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants333
    Cycle 1 Day 1, Pre-Dose
    NA
    (NA)
    Cycle 1 Day 1, 5 Minutes Post-Dose
    23.1
    (3.46)
    31.8
    (12.4)
    Cycle 1 Day 2, 24 Hours Post-Dose
    9.50
    (1.73)
    13.0
    (5.34)
    Cycle 1 Day 3, 48 Hours Post-Dose
    5.67
    (0.924)
    12.0
    (16.3)
    Cycle 1 Day 5, 96 Hours Post-Dose
    3.50
    (1.41)
    8.68
    (13.4)
    Cycle 1 Day 14, 312 Hours Post-Dose
    0.844
    (0.309)
    2.19
    (3.44)
    Cycle 2 Day 1, Pre-Dose
    0.149
    (0.128)
    0.395
    (0.322)
    Cycle 2 Day 1, 5-minutes Post-Dose
    25.3
    (7.56)
    32.9
    (9.80)
    Cycle 2 Day 2, 24 Hours Post-Dose
    8.80
    (6.19)
    10.4
    (8.05)
    Cycle 2 Day 3, 48 Hours Post-Dose
    3.70
    (1.95)
    11.4
    (16.8)
    Cycle 2 Day 5, 96 Hours Post-Dose
    2.04
    (1.26)
    9.61
    (17.9)
    Cycle 3 Day 1, Pre-Dose
    0.116
    (0.163)
    0.491
    (0.387)
    Cycle 3 Day 1, 5 minutes Post-Dose
    23.9
    (2.83)
    31.3
    (9.79)
    Cycle 4 Day 1, Pre-dose
    0.218
    (0.271)
    0.691
    (0.492)
    Cycle 4 Day 1, 5 minutes Post-Dose
    22.9
    (4.60)
    30.0
    (12.2)
    Cycle 5 Day 1, Pre-Dose
    0.264
    (0.321)
    0.845
    (0.564)
    Cycle 5 Day 1, 5 minutes Post-Dose
    22.5
    (3.32)
    30.6
    (15.1)
    Cycle 6 Day 1, Pre-Dose
    0.312
    (0.351)
    1.06
    (0.699)
    Cycle 6 Day 1, 5 minutes Post-Dose
    20.3
    (4.38)
    33.2
    (16.1)
    Cycle 7 Day 1, Pre-Dose
    0.327
    (0.337)
    1.04
    (0.618)
    Cycle 7 Day 1, 5 minutes Post-Dose
    17.9
    (2.40)
    32.3
    (15.4)
    Cycle 8 Day 1, Pre-Dose
    1.25
    (0.565)
    Cycle 8 Day 1, 5 minutes Post-Dose
    35.2
    (10.5)
    Cycle 8 Day 2, 24 Hours Post-Dose
    14.0
    (4.55)
    Cycle 8 Day 3, 48 Hours Post-Dose
    9.53
    (2.96)
    Cycle 8 Day 5, 96 Hours Post-Dose
    6.44
    (2.35)
    Cycle 8 Day 14, 312 Hours Post-Dose
    3.30
    (4.63)
    Cycle 9 Day 1, Pre-Dose
    4.37
    (11.7)
    Cycle 9 Day 1, 5 Minutes Post-Dose
    29.6
    (11.3)
    Cycle 10 Day 1, Pre-Dose
    1.20
    (0.455)
    Cycle 10 Day 1, 5 minutes Post-Dose
    35.7
    (9.50)
    Cycle 11 Day 1, Pre-Dose
    1.84
    (1.57)
    Cycle 11 Day 1, 5 minutes Post-Dose
    35.7
    (10.8)
    Cycle 12 Day 1, Pre-Dose
    1.47
    (0.665)
    Cycle 12 Day 1, 5 minutes Post-Dose
    40.0
    (10.4)
    Cycle 13 Day 1, Pre-Dose
    6.28
    (11.5)
    Cycle 13 Day 1, 5 minutes Post-Dose
    33.3
    (16.1)
    Cycle 14 Day 1, Pre-Dose
    1.60
    (0.600)
    Cycle 14 Day 1, 5 minutes Post-Dose
    37.0
    (7.92)
    Cycle 15 Day 1, Pre-Dose
    1.48
    (0.542)
    Cycle 15 Day 1, 5 minutes Post-Dose
    40.3
    (10.6)
    Cycle 16 Day 1, Pre-Dose
    1.52
    (0.361)
    Cycle 16 Day 1, 5 minutes Post-Dose
    41.5
    (4.70)
    20. Secondary Outcome
    TitleSerum Concentration of Total Antibodies (Conjugated and Unconjugated)
    DescriptionBlood samples were collected and tested for conjugated and unconjugated antibodies.
    Time FrameCycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

    Outcome Measure Data

    Analysis Population Description
    PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants333
    Cycle 1 Day 1, Pre-Dose
    NA
    (NA)
    NA
    (NA)
    Cycle 1 Day 1, 5 Minutes Post-Dose
    26.3
    (2.29)
    34.7
    (13.4)
    Cycle 1 Day 2, 24 Hours Post-Dose
    16.7
    (1.50)
    25.0
    (9.59)
    Cycle 1 Day 3, 48 Hours Post-Dose
    12.7
    (3.13)
    18.5
    (7.57)
    Cycle 1 Day 5, 96 Hours Post-Dose
    8.63
    (5.11)
    11.8
    (5.02)
    Cycle 1 Day 14, 312 Hours Post-Dose
    2.23
    (0.833)
    3.50
    (1.70)
    Cycle 2 Day 1, Pre-Dose
    0.470
    (0.459)
    1.16
    (0.825)
    Cycle 2 Day 1, 5-minutes Post-Dose
    26.9
    (7.98)
    35.6
    (12.0)
    Cycle 2 Day 2, 24 Hours Post-Dose
    17.1
    (10.4)
    17.2
    (7.93)
    Cycle 2 Day 3, 48 Hours Post-Dose
    9.60
    (5.39)
    16.0
    (6.73)
    Cycle 2 Day 3, 96 Hours Post-Dose
    6.43
    (3.69)
    10.2
    (5.16)
    Cycle 3 Day 1, Pre-Dose
    0.415
    (0.586)
    1.62
    (1.07)
    Cycle 3 Day 1, 5 minutes Post-Dose
    30.0
    (5.87)
    38.2
    (13.1)
    Cycle 4 Day 1, Pre-dose
    0.875
    (1.03)
    1.95
    (1.26)
    Cycle 4 Day 1, 5 minutes Post-Dose
    29.6
    (8.13)
    37.1
    (15.6)
    Cycle 5 Day 1, Pre-Dose
    0.844
    (0.928)
    2.45
    (1.68)
    Cycle 5 Day 1, 5 minutes Post-Dose
    29.4
    (3.04)
    38.0
    (18.8)
    Cycle 6 Day 1, Pre-Dose
    1.05
    (1.20)
    2.99
    (1.81)
    Cycle 6 Day 1, 5 minutes Post-Dose
    29.4
    (5.37)
    39.8
    (19.8)
    Cycle 7 Day 1, Pre-Dose
    0.995
    (0.998)
    2.92
    (1.62)
    Cycle 7 Day 1, 5 minutes Post-Dose
    24.0
    (2.69)
    41.0
    (21.2)
    Cycle 8 Day 1, Pre-Dose
    3.29
    (1.14)
    Cycle 8 Day 1, 5 minutes Post-Dose
    41.4
    (9.47)
    Cycle 8 Day 2, 24 Hours Post-Dose
    28.2
    (6.38)
    Cycle 8 Day 3, 48 Hours Post-Dose
    22.9
    (5.67)
    Cycle 8 Day 5, 96 Hours Post-Dose
    17.3
    (4.93)
    Cycle 8 Day 14, 312 Hours Post-Dose
    5.74
    (2.02)
    Cycle 9 Day 1, Pre-Dose
    6.30
    (12.0)
    Cycle 9 Day 1, 5 Minutes Post-Dose
    35.1
    (11.3)
    Cycle 10 Day 1, Pre-Dose
    3.48
    (1.13)
    Cycle 10 Day 1, 5 minutes Post-Dose
    41.4
    (8.63)
    Cycle 11 Day 1, Pre-Dose
    3.96
    (2.24)
    Cycle 11 Day 1, 5 minutes Post-Dose
    42.8
    (8.85)
    Cycle 12 Day 1, Pre-Dose
    3.47
    (1.28)
    Cycle 12 Day 1, 5 minutes Post-Dose
    44.8
    (10.3)
    Cycle 13 Day 1, Pre-Dose
    11.3
    (17.1)
    Cycle 13 Day 1, 5 minutes Post-Dose
    NA
    (NA)
    40.3
    (19.2)
    Cycle 14 Day 1, Pre-Dose
    3.97
    (1.14)
    Cycle 14 Day 1, 5 minutes Post-Dose
    44.5
    (7.05)
    Cycle 15 Day 1, Pre-Dose
    4.02
    (1.40)
    Cycle 15 Day 1, 5 minutes Post-Dose
    49.7
    (6.88)
    Cycle 16 Day 1, Pre-Dose
    4.60
    (1.67)
    Cycle 16 Day 1, 5 minutes Post-Dose
    49.7
    (7.61)
    21. Secondary Outcome
    TitleMonomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2)
    DescriptionBlood samples were collected and tested for MMAE plasma concentrations.
    Time FrameCycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

    Outcome Measure Data

    Analysis Population Description
    PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm.
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    Measure Participants333
    Cycle 1 Day 1, Pre-Dose
    NA
    (NA)
    NA
    (NA)
    Cycle 1 Day 1, 5 Minutes Post-Dose
    0.416
    (0.480)
    0.368
    (0.309)
    Cycle 1 Day 2, 24 Hours Post-Dose
    4.63
    (3.20)
    4.88
    (3.55)
    Cycle 1 Day 3, 48 Hours Post-Dose
    4.20
    (1.95)
    5.36
    (3.72)
    Cycle 1 Day 5, 96 Hours Post-Dose
    2.80
    (0.300)
    4.43
    (3.04)
    Cycle 1 Day 14, 312 Hours Post-Dose
    0.196
    (0.0641)
    0.530
    (0.552)
    Cycle 2 Day 1, Pre-Dose
    0.0647
    (0.0358)
    0.0739
    (0.0640)
    Cycle 2 Day 1, 5-minutes Post-Dose
    0.556
    (0.562)
    0.478
    (0.461)
    Cycle 2 Day 2, 24 Hours Post-Dose
    5.63
    (5.72)
    3.71
    (3.94)
    Cycle 2 Day 3, 48 Hours Post-Dose
    4.60
    (3.70)
    3.86
    (3.18)
    Cycle 2 Day 5, 96 Hours Post-Dose
    2.60
    (1.04)
    2.70
    (1.69)
    Cycle 3 Day 1, Pre-Dose
    0.0250
    (0.0354)
    0.0650
    (0.0590)
    Cycle 3 Day 1, 5 minutes Post-Dose
    0.216
    (0.0361)
    0.514
    (0.684)
    Cycle 4 Day 1, Pre-dose
    0.0565
    (0.00495)
    0.0866
    (0.0784)
    Cycle 4 Day 1, 5 minutes Post-Dose
    0.234
    (0.0742)
    0.376
    (0.449)
    Cycle 5 Day 1, Pre-Dose
    0.0820
    (NA)
    0.0862
    (0.0729)
    Cycle 5 Day 1, 5 minutes Post-Dose
    0.334
    (0.0955)
    0.301
    (0.248)
    Cycle 6 Day 1, Pre-Dose
    0.0680
    (0.0156)
    0.0841
    (0.0632)
    Cycle 6 Day 1, 5 minutes Post-Dose
    0.247
    (0.00707)
    0.450
    (0.663)
    Cycle 7 Day 1, Pre-Dose
    0.104
    (0.0389)
    0.0830
    (0.0578)
    Cycle 7 Day 1, 5 minutes Post-Dose
    0.326
    (0.0361)
    0.310
    (0.282)
    Cycle 8 Day 1, Pre-Dose
    0.101
    (0.934)
    Cycle 8 Day 1, 5 minutes Post-Dose
    0.295
    (0.151)
    Cycle 8 Day 2, 24 Hours Post-Dose
    1.96
    (1.31)
    Cycle 8 Day 3, 48 Hours Post-Dose
    1.91
    (1.29)
    Cycle 8 Day 5, 96 Hours Post-Dose
    2.00
    (1.05)
    Cycle 8 Day 14, 312 Hours Post-Dose
    0.325
    (0.214)
    Cycle 9 Day 1, Pre-Dose
    0.0819
    (0.0496)
    Cycle 9 Day 1, 5 Minutes Post-Dose
    0.218
    (0.128)
    Cycle 10 Day 1, Pre-Dose
    0.727
    (0.0517)
    Cycle 10 Day 1, 5 minutes Post-Dose
    0.204
    (0.0982)
    Cycle 11 Day 1, Pre-Dose
    0.0763
    (0.0368)
    Cycle 11 Day 1, 5 minutes Post-Dose
    0.255
    (0.133)
    Cycle 12 Day 1, Pre-Dose
    0.105
    (0.0983)
    Cycle 12 Day 1, 5 minutes Post-Dose
    0.252
    (0.116)
    Cycle 13 Day 1, Pre-Dose
    0.110
    (0.0629)
    Cycle 13 Day 1, 5 minutes Post-Dose
    0.244
    (0.130)
    Cycle 14 Day 1, Pre-Dose
    0.109
    (0.0529)
    Cycle 14 Day 1, 5 minutes Post-Dose
    0.320
    (0.138)
    Cycle 15 Day 1, Pre-Dose
    0.0843
    (0.0548)
    Cycle 15 Day 1, 5 minutes Post-Dose
    0.404
    (0.192)
    Cycle 16 Day 1, Pre-Dose
    0.139
    (0.0926)
    Cycle 16 Day 1, 5 minutes Post-Dose
    0.381
    (0.277)

    Adverse Events

    Time FrameFrom the first dose through 30 days after the last dose of study medication (Up to 15 months)
    Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. At the time of study completion, a total of 9 deaths were reported for the safety population, 1 on study death (death within 30 days of last dose) and 8 deaths during post-treatment follow up (PTFU).
    Arm/Group TitleBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Arm/Group DescriptionBrentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.
    All Cause Mortality
    Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/3 (33.3%) 6/16 (37.5%) 2/17 (11.8%)
    Serious Adverse Events
    Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/3 (0%) 7/16 (43.8%) 1/17 (5.9%)
    Blood and lymphatic system disorders
    Febrile neutropenia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Cardiac disorders
    Supraventricular tachycardia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Cardiac arrest0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Gastrointestinal disorders
    Vomiting0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    General disorders
    Pyrexia0/3 (0%) 1/16 (6.3%) 1/17 (5.9%)
    Myalgia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Hepatobiliary disorders
    Hepatotoxicity0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Immune system disorders
    Anaphylactic reaction0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Infections and infestations
    Pneumonia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Other (Not Including Serious) Adverse Events
    Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 16/16 (100%) 17/17 (100%)
    Blood and lymphatic system disorders
    Neutropenia0/3 (0%) 4/16 (25%) 1/17 (5.9%)
    Lymph node pain0/3 (0%) 2/16 (12.5%) 1/17 (5.9%)
    Lymphadenopathy0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Anaemia0/3 (0%) 2/16 (12.5%) 0/17 (0%)
    Leukopenia0/3 (0%) 2/16 (12.5%) 0/17 (0%)
    Thrombocytopenia0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Cardiac disorders
    Angina pectoris0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Sinus tachycardia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Ear and labyrinth disorders
    Tinnitus0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Eye disorders
    Eye discharge0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Gastrointestinal disorders
    Nausea2/3 (66.7%) 7/16 (43.8%) 4/17 (23.5%)
    Vomiting0/3 (0%) 2/16 (12.5%) 3/17 (17.6%)
    Abdominal pain upper1/3 (33.3%) 2/16 (12.5%) 1/17 (5.9%)
    Abdominal pain1/3 (33.3%) 2/16 (12.5%) 0/17 (0%)
    Gastrointestinal pain0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Diarrhoea0/3 (0%) 2/16 (12.5%) 3/17 (17.6%)
    Constipation0/3 (0%) 2/16 (12.5%) 0/17 (0%)
    Gastrooesophageal reflux disease0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Gastritis0/3 (0%) 1/16 (6.3%) 1/17 (5.9%)
    Toothache0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Dyspepsia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Gastrointestinal motility disorder0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Dysphagia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Odynophagia0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    General disorders
    Pyrexia1/3 (33.3%) 8/16 (50%) 7/17 (41.2%)
    Fatigue0/3 (0%) 2/16 (12.5%) 1/17 (5.9%)
    Asthenia0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Feeling hot0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Oedema peripheral0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Hepatobiliary disorders
    Hepatotoxicity0/3 (0%) 2/16 (12.5%) 0/17 (0%)
    Hypertransaminasaemia0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Hepatic pain0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Infections and infestations
    Rhinitis0/3 (0%) 3/16 (18.8%) 4/17 (23.5%)
    Pharyngitis0/3 (0%) 3/16 (18.8%) 3/17 (17.6%)
    Nasopharyngitis0/3 (0%) 1/16 (6.3%) 1/17 (5.9%)
    Sinusitis0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Upper respiratory tract infection1/3 (33.3%) 0/16 (0%) 0/17 (0%)
    Gingivitis0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Tooth abscess0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Clostridium difficile colitis0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Conjunctivitis0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Vulvovaginal mycotic infection0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Herpes zoster0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Influenza0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Respiratory syncytial virus infection0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Paronychia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Injury, poisoning and procedural complications
    Joint dislocation0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Muscle strain1/3 (33.3%) 0/16 (0%) 0/17 (0%)
    Head injury0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Facial bones fracture0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Investigations
    Gamma-glutamyltransferase increased0/3 (0%) 2/16 (12.5%) 0/17 (0%)
    Alanine aminotransferase increased0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Aspartate aminotransferase increased0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Transaminases increased0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Lymphocyte count decreased1/3 (33.3%) 0/16 (0%) 2/17 (11.8%)
    Neutrophil count decreased0/3 (0%) 0/16 (0%) 2/17 (11.8%)
    White blood cell count decreased0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Blood bicarbonate decreased0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Weight decreased0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    C-reactive protein increased0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Blood alkaline phosphatase increased0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Metabolism and nutrition disorders
    Decreased appetite0/3 (0%) 3/16 (18.8%) 0/17 (0%)
    Hypokalaemia0/3 (0%) 2/16 (12.5%) 1/17 (5.9%)
    Hyperuricaemia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Hypophosphataemia0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Hypoalbuminaemia0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity0/3 (0%) 2/16 (12.5%) 1/17 (5.9%)
    Musculoskeletal pain0/3 (0%) 2/16 (12.5%) 0/17 (0%)
    Back pain0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Neck pain0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Myalgia0/3 (0%) 4/16 (25%) 0/17 (0%)
    Arthralgia1/3 (33.3%) 1/16 (6.3%) 0/17 (0%)
    Muscle spasms0/3 (0%) 1/16 (6.3%) 1/17 (5.9%)
    Groin pain0/3 (0%) 1/16 (6.3%) 1/17 (5.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain1/3 (33.3%) 0/16 (0%) 0/17 (0%)
    Nervous system disorders
    Paraesthesia1/3 (33.3%) 5/16 (31.3%) 1/17 (5.9%)
    Peripheral sensory neuropathy0/3 (0%) 2/16 (12.5%) 2/17 (11.8%)
    Neuropathy peripheral0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Peripheral motor neuropathy0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Headache0/3 (0%) 0/16 (0%) 3/17 (17.6%)
    Migraine0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Dysgeusia1/3 (33.3%) 0/16 (0%) 0/17 (0%)
    Tremor0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Vocal cord paralysis0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Psychiatric disorders
    Insomnia0/3 (0%) 1/16 (6.3%) 1/17 (5.9%)
    Anxiety0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Renal and urinary disorders
    Pollakiuria0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Urinary tract pain0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Reproductive system and breast disorders
    Menstruation irregular0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough0/3 (0%) 3/16 (18.8%) 1/17 (5.9%)
    Oropharyngeal pain0/3 (0%) 2/16 (12.5%) 0/17 (0%)
    Dyspnoea0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Skin and subcutaneous tissue disorders
    Rash0/3 (0%) 1/16 (6.3%) 1/17 (5.9%)
    Rash maculo-papular0/3 (0%) 0/16 (0%) 2/17 (11.8%)
    Blister0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Dermatosis0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Dry skin0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Pruritus0/3 (0%) 2/16 (12.5%) 0/17 (0%)
    Urticaria0/3 (0%) 1/16 (6.3%) 1/17 (5.9%)
    Alopecia0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Night sweats0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Seborrhoeic dermatitis0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Drug eruption1/3 (33.3%) 0/16 (0%) 0/17 (0%)
    Erythema0/3 (0%) 0/16 (0%) 1/17 (5.9%)
    Erythema multiforme0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Vascular disorders
    Haematoma0/3 (0%) 1/16 (6.3%) 0/17 (0%)
    Flushing0/3 (0%) 0/16 (0%) 1/17 (5.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.

    Results Point of Contact

    Name/TitleMedical Director
    OrganizationTakeda
    Phone+1-877-825-3327
    Emailtrialdisclosures@takeda.com
    Responsible Party:
    Millennium Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT01492088
    Other Study ID Numbers:
    • C25002
    • 2011-001240-29
    • U1111-1158-2613
    • 133300410A0384
    • NL38209.078.11
    First Posted:
    Dec 14, 2011
    Last Update Posted:
    Nov 20, 2018
    Last Verified:
    Nov 1, 2018