A Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Participants With Advanced Stage Newly Diagnosed Hodgkin Lymphoma

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT02979522
Collaborator
(none)
59
Enrollment
14
Locations
1
Arm
48.6
Actual Duration (Months)
4.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as confirm the recommended dose of brentuximab vedotin (ADCETRIS) in combination with a multiagent chemotherapy regimen, doxorubicin (Adriamycin), vinblastine, and dacarbazine, in pediatric participants with advanced stage newly diagnosed classical CD30+ Hodgkin Lymphoma (HL).

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Detailed Description

The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat pediatric participants who have advanced stage, newly diagnosed, classical CD30+ HL. This study will assess the safety, tolerability, and anti-tumor activity, as well as recommended dose of brentuximab vedotin in combination with a multiagent chemotherapy regimen that is based on a current standard of care (SOC) first-line treatment regimen for newly diagnosed HL.

The study will enroll at least 55 evaluable participants. The study will be conducted in 2 phases, Phase 1 and Phase 2. Phase 1 study will enroll at least 6 participants to determine the recommended dose. Once the recommended dose is identified additional participants will be enrolled into phase 2 so that the total number of evaluable participants will be at least 55, including participants treated at recommended dose in Phase 1. Participants will be enrolled to the following initial dose cohort with an option to explore a reduced dose cohort at 36 mg/m^2 if needed:

• Brentuximab vedotin 48 mg/m^2 in combination with doxorubicin, vinblastine, and dacarbazine.

Participants continue in follow-up to Sept 2021 and may continue in the optional long-term follow-up of approximately 10 years up to Sept 2029.

This multi-center trial will be conducted in the United States, Italy, Brazil and Japan. The overall time to participate in this study is approximately 55 months, including the follow-up period. Participants will be followed for a maximum of 30 days following the last dose of protocol therapy for a follow-up assessment and will be followed for survival and disease status every 12 weeks for 12 months, and then every 24 weeks until death or study closure or for up to 2 years from the date of the last participant enrolled. All participants will have an opportunity to participate in an optional long-term follow up, for at least 10 years from their date of enrollment in the main study.

Study Design

Study Type:
Interventional
Actual Enrollment :
59 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Patients With Advanced Stage Newly Diagnosed Hodgkin Lymphoma
Actual Study Start Date :
Sep 6, 2017
Actual Primary Completion Date :
May 5, 2020
Actual Study Completion Date :
Sep 24, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Brentuximab vedotin 48 mg/m^2

Brentuximab vedotin 48 milligram per square meter (mg/m^2), intravenous infusion, once on Day 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and Dacarbazine 375 mg/m^2, intravenous infusion, once on Day 1 and 15 of each 28-day cycle for up to 6 cycles. If the first 6 participants complete the dose limiting toxicity (DLT) observation period with 0 or 1 participant experiencing a DLT, 48 mg/m^2 will be established as the recommended dose for phase 2 study. If at any time more than 1 participant out of a maximum 6 DLT-evaluable participants experiences a DLT, brentuximab vedotin dose will be reduced to 36 mg/m^2. If 0 or 1 participant experiences a DLT among the 6 participants treated at 36 mg/m^2, 36 mg/m^2 will be established as recommended dose for phase 2 study. If more than 1 participant experiences a DLT in the first 6 participants treated at 36 mg/m^2, the study will be discontinued.

Drug: Brentuximab vedotin
Brentuximab vedotin infusion
Other Names:
  • Adcetris
  • Drug: Doxorubicin
    Doxorubicin infusion
    Other Names:
  • Adriamycin
  • Drug: Vinblastine
    Vinblastine infusion

    Drug: Dacarbazine
    Dacarbazine infusion

    Outcome Measures

    Primary Outcome Measures

    1. Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population [From the first dose (Cycle 1) up to Day 56 (Cycle length=28 days)]

      The recommended dose was determined after considering all safety data in phase 1 and assessing for dose limiting toxicities (DLTs) which are defined as the dose range at which less than or equal to (<=) 1 of 6 evaluable participants experience DLT within the defined observation period (Cycle 1 + 28 days). This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.

    2. Phase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.

    3. Phase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.

    4. Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit [At end of treatment (EOT) visit 30 days after the last dose of study drug (at Month 7)]

      CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.

    5. Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment [From first dose of study drug up to Cycle 2 Day 25 (Each Cycle length=28 days)]

      The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.

    6. Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit [At EOT visit 30 days after the last dose of study drug (at Month 7)]

      PR was defined as regression of measurable disease and no new sites as assessed by IRF as per IWG criteria. Percentage of participants in the response-evaluable population who achieved a partial response based on the IRF assessment at the EOT visit based on the IWG criteria are reported. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.

    7. Phase 2: Percentage of Participants Who Achieved an Overall Response (OR) Per IRF Assessment Per IWG Criteria at EOT Visit [At EOT visit 30 days after the last dose of study drug (at Month 7)]

      Overall response rate was defined as the percentage of participants with CR or PR as assessed by IRF using IWG criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new diseases. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.

    8. Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose [From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)]

      This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.

    Secondary Outcome Measures

    1. Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin and Total (Free and Conjugated) Therapeutic Antibody (TAb) [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    2. Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE) [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    3. Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    4. Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    5. Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    6. Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    7. Phase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit [At EOT visit 30 days after the last dose of study drug (at Month 7)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    8. Phase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit [At EOT visit 30 days after the last dose of study drug (at Month 7)]

      PR was defined as regression of measurable disease and no new diseases as per IWG Criteria based on IRF. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    9. Phase 1: Percentage of Participants Who Achieved an OR Per IRF Assessment Per IWG Criteria at EOT Visit [At EOT visit 30 days after the last dose of study drug (at Month 7)]

      Overall response rate was defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    10. Phase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment [From first dose of study drug up to Cycle 2 (Each Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    11. Phase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment [From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    12. Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive [Up to 7 months]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    13. Phase 2: Progression-free Survival (PFS) [Up to 24 months]

      PFS per IRF: time from first dose until disease progression per IRF/death due to any cause, whichever occurred first. Participants who did not have objective progressive disease (PD), did not die, were either still on study follow-up at time of analysis were removed from study prior to documentation of PD, PFS were censored on date of last adequate disease assessment before initiation of any non-protocol, alternative therapy. Participants who were on antitumor treatment, other than SCT, or radiotherapy, censoring was at last adequate disease assessment before initiation of such alternative treatment. If participant experienced disease progression per IRF/died after initiation of antitumor treatment, other than SCT, or radiotherapy, such participant were censored and not considered having PFS. Outcome measure is planned to be assessed for all participant treated at RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (September 2021).

    14. Phase 2: Event-free Survival (EFS) [Up to 24 months]

      EFS:Time from the first dose until any treatment failure:PD per IRF including progression events during follow-up period, failing to complete 6 cycles of treatment due to any reason or death due to any cause, whichever occurred first. EFS per IRF were censored on the last adequate disease assessment date per IRF if none of the above events occur during the study.For participants who were given antitumor treatment, other than SCT, or radiotherapy as part of frontline treatment, censoring was done at the last adequate disease assessment before initiation of such alternative treatment.If a participant experienced disease progression per IRF/died after the initiation of antitumor treatment, other than SCT, or radiotherapy, such participant was censored, and not be considered having EFS.This outcome measure is planned to be assessed for all patients treated at the RP2D in Phase 2.Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    15. Phase 2: Overall Survival (OS) [Up to 24 months]

      Overall survival was defined as time from first dose until death. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive, including study closure. This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    16. Phase 2: Duration of Response (DOR) [Up to 24 months]

      DOR per IRF in participants with a response (CR or PR per IRF) was defined as the time from start of the first objective tumor response (CR or PR per IRF) to the first subsequent PD or death due to any cause, whichever occurred first. For patients who did not have an objective PD, did not die and are either still on a study follow-up at the time of the analysis, or were removed from the study prior to documentation of PD, DOR has been censored on the date of last adequate disease assessment. This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    17. Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment [Up to 24 months]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    18. Phase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    19. Phase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    20. Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive [From first dose until 30 days after the last dose of study drug (up to 7 months)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    21. Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    22. Phase 2: Mean Plasma Cmax of MMAE [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    23. Phase 2: Mean Serum AUC0-15 of Brentuximab Vedotin and TAb [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    24. Phase 2: Mean Plasma AUC0-15 of MMAE [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    25. Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    26. Phase 2: Median Tmax of MMAE in Plasma [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    27. Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy [Up to 24 months]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    28. Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events [Up to 24 months]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    29. Phase 2: Immune Reconstitution Over Time [Up to 24 months]

      Immune reconstitution (peripheral blood CD34+ count; enumeration of the total lymphocyte count and lymphocyte subsets; total immunoglobulin and Immunoglobulin (Ig) G, IgM, IgA levels; levels of antibodies to tetanus, hemophilus influenza type B (HiB), and polio serotypes). This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    30. Phase 1: ATA Titer [Up to 6 months]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    31. Phase 2: ATA Titer [Up to 6 months]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    32. Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    33. Phase 1: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    34. Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants [Up to 24 months]

      CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    35. Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs [Up to 24 months]

      This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    36. Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    37. Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    38. Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants [Up to 24 months]

      CR is defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    39. Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs [Up to 24 months]

      This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    5 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Each participant must meet all the following inclusion criteria to be enrolled in the study:

    1. Histologically confirmed CD30+ classical HL.

    2. Advanced stage, newly diagnosed HL (Stage III and Stage IV disease).

    3. Treatment-naive HL.

    4. Have performance scores of greater than or equal to (>=) 50 for Lansky Play-performance or Karnofsky Performance Status.

    5. Have bidimensional measurable disease as documented by radiographic technique per International Working Group (IWG) criteria.

    6. Have adequate blood counts, renal and liver function as defined in the protocol.

    Exclusion Criteria:
    1. Nodular lymphocyte predominant HL.

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

    3. Any sensory or motor peripheral neuropathy.

    4. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.

    5. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks before the first study protocol therapy.

    6. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of AVD.

    7. Known human immunodeficiency virus positive.

    8. Known hepatitis B surface antigen positive or known or suspected active hepatitis C infection, as determined by hepatitis B DNA or hepatitis C RNA, respectively, in blood.

    9. Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

    10. Use of any strong or listed moderate cytochrome P450 (CYP) 3A4 inhibitors less than (<) 2 weeks before the first dose of protocol therapy (please refer to the Study Manual for an example list of prohibited CYP3A4 inhibitors).

    11. Any of the following cardiovascular conditions or values within 6 months before the first dose of protocol therapy:

    • Shortening fraction of <27 percent (%) by echocardiogram or, if echocardiogram not feasible, ejection fraction of <50% by radionuclide angiogram (RNA or MUGA [multiple-gated acquisition scan]).

    • New York Heart Association Class III or IV heart failure.

    • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Children's Hospital ColoradoAuroraColoradoUnited States80045
    2Cincinnati Children's Hospital Medical CenterCincinnatiOhioUnited States45229
    3Hospital Sao Rafael S/ASalvadorBahiaBrazil41253-190
    4Jardim das AmericasParanaBrazil81520-060
    5INCA - Instituto Nacional de CancerRio de JaneiroBrazil20230-230
    6GRAACC - Grupo de Apoio ao Adolescente e a Crianca com CancerSao PauloBrazil04023-062
    7ICr - Instituto da Crianca - HCFMUSPSao PauloBrazil05403-000
    8Hospital Santa MarcelinaSao PauloBrazil08270-070
    9Azienda Ospedaliero Universitaria Ospedale Pediatrico MeyerFirenzeItaly50139
    10Fondazione IRCCS Policlinico San MatteoPaviaItaly27100
    11Ospedale Pediatrico Bambino Gesu,UOC Onco-ematologiaRomaItaly165
    12Azienda Ospedaliera Citta della Salute e della Scienza di TorinoTorinoItaly10126
    13NHO Nagoya Medical CenterNagoya-shiAichi-KenJapan460-0001
    14St. Marianna University School of Medicine HospitalKawasaki-shiKanagawa-KenJapan216-8511

    Sponsors and Collaborators

    • Takeda

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT02979522
    Other Study ID Numbers:
    • C25004
    • 2015-004112-38
    • U1111-1171-0984
    First Posted:
    Dec 1, 2016
    Last Update Posted:
    Oct 22, 2021
    Last Verified:
    Oct 1, 2021
    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 Takeda
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants took part in the study at 14 investigative sites in the United States, Italy, Brazil and Japan. Results are reported based on the primary completion date (05 May 2020) of the study.
    Pre-assignment DetailParticipants with advanced stage newly diagnosed, classical CD30+ Hodgkin Lymphoma (HL) were enrolled in this 2-phase study to receive brentuximab vedotin 48 milligram per square meter (mg/m^2) in combination with doxorubicin, vinblastine, and dacarbazine (A+AVD). Phase 2 included all participants treated in Phase 1 along with additional enrolled participants in Phase 2. As planned, 36 mg/m^2 group was omitted from the study since no participant received 36 mg/m^2.
    Arm/Group TitlePhase 1:Brentuximab Vedotin 48 mg/m^2 + AVDPhase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Period Title: Period 1: Phase 1
    STARTED80
    COMPLETED80
    NOT COMPLETED00
    Period Title: Period 1: Phase 1
    STARTED059
    COMPLETED059
    NOT COMPLETED00

    Baseline Characteristics

    Arm/Group TitlePhase 1: Brentuximab Vedotin 48 mg/m^2 +AVDPhase 2: Brentuximab Vedotin 48 mg/m^2 + AVDTotal
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.Total of all reporting groups
    Overall Participants85159
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    12.4
    (3.81)
    13.9
    (2.88)
    13.7
    (3.03)
    Sex: Female, Male (Count of Participants)
    Female
    4
    50%
    24
    47.1%
    28
    47.5%
    Male
    4
    50%
    27
    52.9%
    31
    52.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    25%
    21
    41.2%
    23
    39%
    Not Hispanic or Latino
    6
    75%
    26
    51%
    32
    54.2%
    Unknown or Not Reported
    0
    0%
    4
    7.8%
    4
    6.8%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    0
    0%
    3
    5.9%
    3
    5.1%
    Black or African American
    0
    0%
    12
    23.5%
    12
    20.3%
    White
    8
    100%
    26
    51%
    34
    57.6%
    "Brown" or "Mulatto"
    0
    0%
    9
    17.6%
    9
    15.3%
    Unknown or Not Reported
    0
    0%
    1
    2%
    1
    1.7%
    Region of Enrollment (Count of Participants)
    United States
    2
    25%
    10
    19.6%
    12
    20.3%
    Japan
    0
    0%
    2
    3.9%
    2
    3.4%
    Italy
    5
    62.5%
    10
    19.6%
    15
    25.4%
    Brazil
    1
    12.5%
    29
    56.9%
    30
    50.8%
    Weight (kilogram (kg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilogram (kg)]
    45.91
    (18.867)
    49.91
    (15.649)
    49.37
    (16.000)

    Outcome Measures

    1. Primary Outcome
    TitlePhase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population
    DescriptionThe recommended dose was determined after considering all safety data in phase 1 and assessing for dose limiting toxicities (DLTs) which are defined as the dose range at which less than or equal to (<=) 1 of 6 evaluable participants experience DLT within the defined observation period (Cycle 1 + 28 days). This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
    Time FrameFrom the first dose (Cycle 1) up to Day 56 (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    The DLT-evaluable population included participants who had received at least 1 dose of study drug therapy and experienced a DLT or no DLT during the DLT observation period. Participants who received granulocyte colony stimulating factor (G-CSF) during the DLT observation period were excluded from the DLT-Evaluable Population.
    Arm/Group TitlePhase 1: Brentuximab Vedotin 48 mg/m^2 +AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Measure Participants6
    Number [mg/m^2]
    48
    2. Primary Outcome
    TitlePhase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
    Time FrameFrom first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
    Arm/Group TitlePhase 1: Brentuximab Vedotin 48 mg/m^2 +AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Measure Participants8
    Number [percentage of participants]
    100
    1250%
    3. Primary Outcome
    TitlePhase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
    Time FrameFrom first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
    Arm/Group TitlePhase 1: Brentuximab Vedotin 48 mg/m^2 +AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Measure Participants8
    Number [percentage of participants]
    13
    162.5%
    4. Primary Outcome
    TitlePhase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit
    DescriptionCR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.
    Time FrameAt end of treatment (EOT) visit 30 days after the last dose of study drug (at Month 7)

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
    Arm/Group TitlePhase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Measure Participants59
    Number (95% Confidence Interval) [percentage of participants]
    76
    950%
    5. Primary Outcome
    TitlePhase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
    DescriptionThe Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.
    Time FrameFrom first dose of study drug up to Cycle 2 Day 25 (Each Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
    Arm/Group TitlePhase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Measure Participants59
    Number [percentage of participants]
    90
    1125%
    6. Primary Outcome
    TitlePhase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit
    DescriptionPR was defined as regression of measurable disease and no new sites as assessed by IRF as per IWG criteria. Percentage of participants in the response-evaluable population who achieved a partial response based on the IRF assessment at the EOT visit based on the IWG criteria are reported. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.
    Time FrameAt EOT visit 30 days after the last dose of study drug (at Month 7)

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
    Arm/Group TitlePhase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Measure Participants59
    Number (95% Confidence Interval) [percentage of participants]
    12
    150%
    7. Primary Outcome
    TitlePhase 2: Percentage of Participants Who Achieved an Overall Response (OR) Per IRF Assessment Per IWG Criteria at EOT Visit
    DescriptionOverall response rate was defined as the percentage of participants with CR or PR as assessed by IRF using IWG criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new diseases. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.
    Time FrameAt EOT visit 30 days after the last dose of study drug (at Month 7)

    Outcome Measure Data

    Analysis Population Description
    Response-evaluable population included participants who received at least one dose of study drug, have measurable disease at baseline, and have at least one post-baseline disease assessment based on an independent review facility.
    Arm/Group TitlePhase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Measure Participants59
    Number (95% Confidence Interval) [percentage of participants]
    88
    1100%
    8. Primary Outcome
    TitlePhase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose
    DescriptionThis outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.
    Time FrameFrom first dose of study drug up to Cycle 6 (Each Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    The safety population included participants who had received at least 1 dose of any study drug (A+AVD regimen).
    Arm/Group TitlePhase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    Measure Participants59
    Number [percentage of participants]
    100
    1250%
    9. Secondary Outcome
    TitlePhase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin and Total (Free and Conjugated) Therapeutic Antibody (TAb)
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    10. Secondary Outcome
    TitlePhase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE)
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    11. Secondary Outcome
    TitlePhase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    12. Secondary Outcome
    TitlePhase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    13. Secondary Outcome
    TitlePhase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    14. Secondary Outcome
    TitlePhase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    15. Secondary Outcome
    TitlePhase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameAt EOT visit 30 days after the last dose of study drug (at Month 7)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    16. Secondary Outcome
    TitlePhase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit
    DescriptionPR was defined as regression of measurable disease and no new diseases as per IWG Criteria based on IRF. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameAt EOT visit 30 days after the last dose of study drug (at Month 7)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    17. Secondary Outcome
    TitlePhase 1: Percentage of Participants Who Achieved an OR Per IRF Assessment Per IWG Criteria at EOT Visit
    DescriptionOverall response rate was defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameAt EOT visit 30 days after the last dose of study drug (at Month 7)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    18. Secondary Outcome
    TitlePhase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameFrom first dose of study drug up to Cycle 2 (Each Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    19. Secondary Outcome
    TitlePhase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameFrom first dose of study drug up to Cycle 6 (Each Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    20. Secondary Outcome
    TitlePhase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 7 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    21. Secondary Outcome
    TitlePhase 2: Progression-free Survival (PFS)
    DescriptionPFS per IRF: time from first dose until disease progression per IRF/death due to any cause, whichever occurred first. Participants who did not have objective progressive disease (PD), did not die, were either still on study follow-up at time of analysis were removed from study prior to documentation of PD, PFS were censored on date of last adequate disease assessment before initiation of any non-protocol, alternative therapy. Participants who were on antitumor treatment, other than SCT, or radiotherapy, censoring was at last adequate disease assessment before initiation of such alternative treatment. If participant experienced disease progression per IRF/died after initiation of antitumor treatment, other than SCT, or radiotherapy, such participant were censored and not considered having PFS. Outcome measure is planned to be assessed for all participant treated at RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    22. Secondary Outcome
    TitlePhase 2: Event-free Survival (EFS)
    DescriptionEFS:Time from the first dose until any treatment failure:PD per IRF including progression events during follow-up period, failing to complete 6 cycles of treatment due to any reason or death due to any cause, whichever occurred first. EFS per IRF were censored on the last adequate disease assessment date per IRF if none of the above events occur during the study.For participants who were given antitumor treatment, other than SCT, or radiotherapy as part of frontline treatment, censoring was done at the last adequate disease assessment before initiation of such alternative treatment.If a participant experienced disease progression per IRF/died after the initiation of antitumor treatment, other than SCT, or radiotherapy, such participant was censored, and not be considered having EFS.This outcome measure is planned to be assessed for all patients treated at the RP2D in Phase 2.Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    23. Secondary Outcome
    TitlePhase 2: Overall Survival (OS)
    DescriptionOverall survival was defined as time from first dose until death. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive, including study closure. This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    24. Secondary Outcome
    TitlePhase 2: Duration of Response (DOR)
    DescriptionDOR per IRF in participants with a response (CR or PR per IRF) was defined as the time from start of the first objective tumor response (CR or PR per IRF) to the first subsequent PD or death due to any cause, whichever occurred first. For patients who did not have an objective PD, did not die and are either still on a study follow-up at the time of the analysis, or were removed from the study prior to documentation of PD, DOR has been censored on the date of last adequate disease assessment. This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    25. Secondary Outcome
    TitlePhase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    26. Secondary Outcome
    TitlePhase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameFrom first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    27. Secondary Outcome
    TitlePhase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameFrom first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    28. Secondary Outcome
    TitlePhase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameFrom first dose until 30 days after the last dose of study drug (up to 7 months)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    29. Secondary Outcome
    TitlePhase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    30. Secondary Outcome
    TitlePhase 2: Mean Plasma Cmax of MMAE
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    31. Secondary Outcome
    TitlePhase 2: Mean Serum AUC0-15 of Brentuximab Vedotin and TAb
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    32. Secondary Outcome
    TitlePhase 2: Mean Plasma AUC0-15 of MMAE
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    33. Secondary Outcome
    TitlePhase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    34. Secondary Outcome
    TitlePhase 2: Median Tmax of MMAE in Plasma
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    35. Secondary Outcome
    TitlePhase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    36. Secondary Outcome
    TitlePhase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    37. Secondary Outcome
    TitlePhase 2: Immune Reconstitution Over Time
    DescriptionImmune reconstitution (peripheral blood CD34+ count; enumeration of the total lymphocyte count and lymphocyte subsets; total immunoglobulin and Immunoglobulin (Ig) G, IgM, IgA levels; levels of antibodies to tetanus, hemophilus influenza type B (HiB), and polio serotypes). This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    38. Secondary Outcome
    TitlePhase 1: ATA Titer
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    39. Secondary Outcome
    TitlePhase 2: ATA Titer
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 6 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    40. Secondary Outcome
    TitlePhase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    41. Secondary Outcome
    TitlePhase 1: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    42. Secondary Outcome
    TitlePhase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
    DescriptionCR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    43. Secondary Outcome
    TitlePhase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
    DescriptionThis outcome measure is planned to be assessed only for participants treated in Phase 1 arm. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    44. Secondary Outcome
    TitlePhase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    45. Secondary Outcome
    TitlePhase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameCycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    46. Secondary Outcome
    TitlePhase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
    DescriptionCR is defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. This outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    47. Secondary Outcome
    TitlePhase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
    DescriptionThis outcome measure was planned to be assessed only for all participants treated at the RP2D in Phase 2. Data for this secondary outcome measure will be reported after study completion date (which is September 2021).
    Time FrameUp to 24 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time FrameTreatment-emergent adverse events are adverse events that started from first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
    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.
    Arm/Group TitlePhase 1: Brentuximab Vedotin 48 mg/m^2 + AVDPhase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
    Arm/Group DescriptionBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    All Cause Mortality
    Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVDPhase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/8 (0%) 0/59 (0%)
    Serious Adverse Events
    Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVDPhase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/8 (12.5%) 24/59 (40.7%)
    Blood and lymphatic system disorders
    Febrile neutropenia1/8 (12.5%) 110/59 (16.9%) 18
    Neutropenia0/8 (0%) 03/59 (5.1%) 3
    Anaemia0/8 (0%) 01/59 (1.7%) 1
    Cardiac disorders
    Intracardiac thrombus0/8 (0%) 01/59 (1.7%) 1
    Gastrointestinal disorders
    Vomiting0/8 (0%) 03/59 (5.1%) 4
    Constipation0/8 (0%) 02/59 (3.4%) 2
    Gastrointestinal disorder0/8 (0%) 02/59 (3.4%) 2
    Abdominal pain0/8 (0%) 01/59 (1.7%) 2
    Nausea0/8 (0%) 02/59 (3.4%) 2
    Abdominal pain upper0/8 (0%) 01/59 (1.7%) 1
    Colitis0/8 (0%) 01/59 (1.7%) 1
    Ileus0/8 (0%) 01/59 (1.7%) 2
    General disorders
    Pyrexia0/8 (0%) 02/59 (3.4%) 2
    Mucosal inflammation0/8 (0%) 01/59 (1.7%) 1
    Infections and infestations
    Sepsis0/8 (0%) 02/59 (3.4%) 2
    Bacteraemia0/8 (0%) 01/59 (1.7%) 1
    Device related infection0/8 (0%) 01/59 (1.7%) 1
    Herpes zoster0/8 (0%) 01/59 (1.7%) 1
    Lip infection0/8 (0%) 01/59 (1.7%) 1
    Pneumonia0/8 (0%) 01/59 (1.7%) 1
    Skin infection0/8 (0%) 01/59 (1.7%) 1
    Investigations
    Neutrophil count decreased0/8 (0%) 01/59 (1.7%) 7
    White blood cell count decreased0/8 (0%) 01/59 (1.7%) 1
    Metabolism and nutrition disorders
    Dehydration0/8 (0%) 01/59 (1.7%) 1
    Hyperuricaemia0/8 (0%) 01/59 (1.7%) 1
    Nervous system disorders
    Peripheral motor neuropathy0/8 (0%) 01/59 (1.7%) 1
    Posterior reversible encephalopathy syndrome0/8 (0%) 01/59 (1.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome0/8 (0%) 01/59 (1.7%) 1
    Dyspnoea0/8 (0%) 01/59 (1.7%) 1
    Hypoxia0/8 (0%) 01/59 (1.7%) 1
    Pneumothorax0/8 (0%) 01/59 (1.7%) 2
    Pulmonary embolism0/8 (0%) 01/59 (1.7%) 1
    Vascular disorders
    Venous thrombosis0/8 (0%) 01/59 (1.7%) 1
    Other (Not Including Serious) Adverse Events
    Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVDPhase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total8/8 (100%) 59/59 (100%)
    Blood and lymphatic system disorders
    Neutropenia5/8 (62.5%) 4033/59 (55.9%) 210
    Anaemia1/8 (12.5%) 113/59 (22%) 28
    Leukopenia1/8 (12.5%) 26/59 (10.2%) 9
    Thrombocytopenia1/8 (12.5%) 12/59 (3.4%) 2
    Cardiac disorders
    Sinus tachycardia0/8 (0%) 05/59 (8.5%) 6
    Palpitations1/8 (12.5%) 11/59 (1.7%) 1
    Eye disorders
    Conjunctival hyperaemia1/8 (12.5%) 12/59 (3.4%) 2
    Eyelid oedema1/8 (12.5%) 11/59 (1.7%) 1
    Gastrointestinal disorders
    Vomiting8/8 (100%) 6550/59 (84.7%) 204
    Nausea8/8 (100%) 2444/59 (74.6%) 131
    Abdominal pain2/8 (25%) 223/59 (39%) 42
    Stomatitis4/8 (50%) 622/59 (37.3%) 30
    Constipation4/8 (50%) 621/59 (35.6%) 37
    Diarrhoea4/8 (50%) 514/59 (23.7%) 25
    Abdominal pain upper3/8 (37.5%) 510/59 (16.9%) 12
    Oral pain1/8 (12.5%) 18/59 (13.6%) 8
    Odynophagia2/8 (25%) 25/59 (8.5%) 6
    Dyspepsia1/8 (12.5%) 13/59 (5.1%) 3
    Toothache0/8 (0%) 03/59 (5.1%) 3
    Mouth ulceration1/8 (12.5%) 12/59 (3.4%) 2
    General disorders
    Pyrexia4/8 (50%) 524/59 (40.7%) 32
    Fatigue3/8 (37.5%) 612/59 (20.3%) 18
    Asthenia5/8 (62.5%) 78/59 (13.6%) 13
    Pain0/8 (0%) 06/59 (10.2%) 7
    Catheter site pain1/8 (12.5%) 14/59 (6.8%) 4
    Chills1/8 (12.5%) 13/59 (5.1%) 4
    Influenza like illness0/8 (0%) 03/59 (5.1%) 4
    Non-cardiac chest pain1/8 (12.5%) 11/59 (1.7%) 1
    Hepatobiliary disorders
    Hepatotoxicity1/8 (12.5%) 11/59 (1.7%) 1
    Infections and infestations
    Rhinitis3/8 (37.5%) 410/59 (16.9%) 13
    Conjunctivitis2/8 (25%) 66/59 (10.2%) 10
    Upper respiratory tract infection1/8 (12.5%) 16/59 (10.2%) 6
    Oral herpes1/8 (12.5%) 25/59 (8.5%) 6
    Pharyngitis1/8 (12.5%) 14/59 (6.8%) 4
    Influenza1/8 (12.5%) 12/59 (3.4%) 2
    Injury, poisoning and procedural complications
    Nail avulsion1/8 (12.5%) 11/59 (1.7%) 1
    Investigations
    White blood cell count decreased5/8 (62.5%) 2125/59 (42.4%) 115
    Neutrophil count decreased4/8 (50%) 1822/59 (37.3%) 96
    Weight decreased1/8 (12.5%) 113/59 (22%) 24
    Lymphocyte count decreased0/8 (0%) 07/59 (11.9%) 32
    Polymerase chain reaction positive1/8 (12.5%) 14/59 (6.8%) 7
    Alanine aminotransferase increased2/8 (25%) 23/59 (5.1%) 3
    Aspartate aminotransferase increased1/8 (12.5%) 72/59 (3.4%) 8
    Gamma-glutamyltransferase increased1/8 (12.5%) 12/59 (3.4%) 2
    Metabolism and nutrition disorders
    Decreased appetite2/8 (25%) 214/59 (23.7%) 23
    Dehydration0/8 (0%) 05/59 (8.5%) 5
    Acidosis1/8 (12.5%) 11/59 (1.7%) 1
    Hyperuricaemia1/8 (12.5%) 11/59 (1.7%) 1
    Hypoalbuminaemia1/8 (12.5%) 11/59 (1.7%) 1
    Musculoskeletal and connective tissue disorders
    Back pain2/8 (25%) 614/59 (23.7%) 22
    Arthralgia1/8 (12.5%) 19/59 (15.3%) 13
    Bone pain0/8 (0%) 08/59 (13.6%) 19
    Pain in extremity2/8 (25%) 38/59 (13.6%) 9
    Myalgia1/8 (12.5%) 16/59 (10.2%) 6
    Pain in jaw0/8 (0%) 06/59 (10.2%) 7
    Groin pain1/8 (12.5%) 13/59 (5.1%) 4
    Muscular weakness0/8 (0%) 03/59 (5.1%) 3
    Musculoskeletal pain2/8 (25%) 23/59 (5.1%) 3
    Spinal pain2/8 (25%) 23/59 (5.1%) 3
    Nervous system disorders
    Headache5/8 (62.5%) 719/59 (32.2%) 27
    Dizziness1/8 (12.5%) 17/59 (11.9%) 8
    Peripheral sensory neuropathy2/8 (25%) 45/59 (8.5%) 8
    Paraesthesia0/8 (0%) 03/59 (5.1%) 3
    Peripheral motor neuropathy0/8 (0%) 03/59 (5.1%) 3
    Dysgeusia1/8 (12.5%) 12/59 (3.4%) 2
    Psychiatric disorders
    Anxiety1/8 (12.5%) 15/59 (8.5%) 5
    Insomnia1/8 (12.5%) 24/59 (6.8%) 5
    Reproductive system and breast disorders
    Pelvic pain1/8 (12.5%) 11/59 (1.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain3/8 (37.5%) 313/59 (22%) 14
    Cough1/8 (12.5%) 19/59 (15.3%) 10
    Nasal congestion2/8 (25%) 47/59 (11.9%) 9
    Rhinitis allergic0/8 (0%) 03/59 (5.1%) 4
    Pharyngeal erythema1/8 (12.5%) 12/59 (3.4%) 2
    Laryngeal pain1/8 (12.5%) 11/59 (1.7%) 1
    Dyspnoea0/8 (0%) 05/59 (8.5%) 6
    Skin and subcutaneous tissue disorders
    Alopecia0/8 (0%) 011/59 (18.6%) 13
    Pruritus0/8 (0%) 07/59 (11.9%) 8
    Rash maculo-papular2/8 (25%) 26/59 (10.2%) 8
    Dermatitis contact1/8 (12.5%) 14/59 (6.8%) 4
    Dry skin1/8 (12.5%) 13/59 (5.1%) 3
    Erythema2/8 (25%) 23/59 (5.1%) 3
    Papule1/8 (12.5%) 13/59 (5.1%) 3
    Rash0/8 (0%) 03/59 (5.1%) 3
    Urticaria0/8 (0%) 03/59 (5.1%) 3
    Dermatitis acneiform1/8 (12.5%) 12/59 (3.4%) 3
    Vascular disorders
    Hyperaemia2/8 (25%) 22/59 (3.4%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.

    Results Point of Contact

    Name/TitleStudy Director
    OrganizationMillennium Pharmaceuticals, Inc.
    Phone+1-877-825-3327
    Emailtrialdisclosures@takeda.com
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT02979522
    Other Study ID Numbers:
    • C25004
    • 2015-004112-38
    • U1111-1171-0984
    First Posted:
    Dec 1, 2016
    Last Update Posted:
    Oct 22, 2021
    Last Verified:
    Oct 1, 2021