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)

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 Disease	Intervention/Treatment	Phase
Hodgkin Disease	Drug: Brentuximab vedotin; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine	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

Arm

Intervention/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

	Site	City	State	Country	Postal Code
1	Children's Hospital Colorado	Aurora	Colorado	United States	80045
2	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
3	Hospital Sao Rafael S/A	Salvador	Bahia	Brazil	41253-190
4	Jardim das Americas	Parana		Brazil	81520-060
5	INCA - Instituto Nacional de Cancer	Rio de Janeiro		Brazil	20230-230
6	GRAACC - Grupo de Apoio ao Adolescente e a Crianca com Cancer	Sao Paulo		Brazil	04023-062
7	ICr - Instituto da Crianca - HCFMUSP	Sao Paulo		Brazil	05403-000
8	Hospital Santa Marcelina	Sao Paulo		Brazil	08270-070
9	Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer	Firenze		Italy	50139
10	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
11	Ospedale Pediatrico Bambino Gesu,UOC Onco-ematologia	Roma		Italy	165
12	Azienda Ospedaliera Citta della Salute e della Scienza di Torino	Torino		Italy	10126
13	NHO Nagoya Medical Center	Nagoya-shi	Aichi-Ken	Japan	460-0001
14	St. Marianna University School of Medicine Hospital	Kawasaki-shi	Kanagawa-Ken	Japan	216-8511

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Dec 10, 2019
• Statistical Analysis Plan - Sep 22, 2020

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: Drug therapy, pediatric Hodgkin disease, frontline Hodgkin disease, advanced stage Hodgkin disease, pediatric lymphoma
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Doxorubicin; Dacarbazine; Vinblastine; Brentuximab Vedotin

Study Results

Participant Flow

Recruitment Details

Participants 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 Detail

Participants 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 Title	Phase 1:Brentuximab Vedotin 48 mg/m^2 + AVD	Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
Arm/Group Description	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.	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
STARTED	8	0
COMPLETED	8	0
NOT COMPLETED	0	0
Period Title: Period 1: Phase 1
STARTED	0	59
COMPLETED	0	59
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD	Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD	Total
Arm/Group Description	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.	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 Participants	8	51	59
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

Title	Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population
Description	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.
Time Frame	From 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 Title	Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD
Arm/Group Description	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.
Measure Participants	6
Number [mg/m^2]	48

2. Primary Outcome

Title	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
Description	This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time Frame	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)

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 Title	Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD
Arm/Group Description	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.
Measure Participants	8
Number [percentage of participants]	100 1250%

3. Primary Outcome

Title	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
Description	This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Time Frame	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)

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 Title	Phase 1: Brentuximab Vedotin 48 mg/m^2 +AVD
Arm/Group Description	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.
Measure Participants	8
Number [percentage of participants]	13 162.5%

4. Primary Outcome

Title	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
Description	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.
Time Frame	At 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 Title	Phase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
Arm/Group Description	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.
Measure Participants	59
Number (95% Confidence Interval) [percentage of participants]	76 950%

5. Primary Outcome

Title	Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
Description	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.
Time Frame	From 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 Title	Phase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
Arm/Group Description	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.
Measure Participants	59
Number [percentage of participants]	90 1125%

6. Primary Outcome

Title	Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit
Description	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.
Time Frame	At 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 Title	Phase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
Arm/Group Description	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.
Measure Participants	59
Number (95% Confidence Interval) [percentage of participants]	12 150%

7. Primary Outcome

Title	Phase 2: Percentage of Participants Who Achieved an Overall Response (OR) Per IRF Assessment Per IWG Criteria at EOT Visit
Description	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.
Time Frame	At 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 Title	Phase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
Arm/Group Description	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.
Measure Participants	59
Number (95% Confidence Interval) [percentage of participants]	88 1100%

8. Primary Outcome

Title	Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose
Description	This outcome measure was planned to be assessed for all participants treated at the RP2D in Phase 2.
Time Frame	From 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 Title	Phase 2: Brentuximab Vedotin 48 mg/m^2 +AVD
Arm/Group Description	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.
Measure Participants	59
Number [percentage of participants]	100 1250%

9. Secondary Outcome

Title	Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin and Total (Free and Conjugated) Therapeutic Antibody (TAb)
Description	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 Frame	Cycle 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

Title	Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE)
Description	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 Frame	Cycle 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

Title	Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb
Description	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 Frame	Cycle 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

Title	Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE
Description	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 Frame	Cycle 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

Title	Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum
Description	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 Frame	Cycle 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

Title	Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma
Description	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 Frame	Cycle 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

Title	Phase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit
Description	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 Frame	At 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

Title	Phase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit
Description	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).
Time Frame	At 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

Title	Phase 1: Percentage of Participants Who Achieved an OR Per IRF Assessment Per IWG Criteria at EOT Visit
Description	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).
Time Frame	At 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

Title	Phase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
Description	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 Frame	From 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

Title	Phase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment
Description	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 Frame	From 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

Title	Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive
Description	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 Frame	Up to 7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

21. Secondary Outcome

Title	Phase 2: Progression-free Survival (PFS)
Description	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).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Secondary Outcome

Title	Phase 2: Event-free Survival (EFS)
Description	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).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

23. Secondary Outcome

Title	Phase 2: Overall Survival (OS)
Description	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).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

24. Secondary Outcome

Title	Phase 2: Duration of Response (DOR)
Description	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).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Secondary Outcome

Title	Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment
Description	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 Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

26. Secondary Outcome

Title	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
Description	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 Frame	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

27. Secondary Outcome

Title	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
Description	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 Frame	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

28. Secondary Outcome

Title	Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive
Description	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 Frame	From 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

Title	Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb
Description	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 Frame	Cycle 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

Title	Phase 2: Mean Plasma Cmax of MMAE
Description	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 Frame	Cycle 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

Title	Phase 2: Mean Serum AUC0-15 of Brentuximab Vedotin and TAb
Description	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 Frame	Cycle 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

Title	Phase 2: Mean Plasma AUC0-15 of MMAE
Description	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 Frame	Cycle 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

Title	Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum
Description	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 Frame	Cycle 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

Title	Phase 2: Median Tmax of MMAE in Plasma
Description	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 Frame	Cycle 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

Title	Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy
Description	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 Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

36. Secondary Outcome

Title	Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events
Description	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 Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

37. Secondary Outcome

Title	Phase 2: Immune Reconstitution Over Time
Description	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).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

38. Secondary Outcome

Title	Phase 1: ATA Titer
Description	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 Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

39. Secondary Outcome

Title	Phase 2: ATA Titer
Description	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 Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

40. Secondary Outcome

Title	Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Description	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 Frame	Cycle 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

Title	Phase 1: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Description	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 Frame	Cycle 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

Title	Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
Description	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).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

43. Secondary Outcome

Title	Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
Description	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 Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

44. Secondary Outcome

Title	Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Description	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 Frame	Cycle 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

Title	Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Description	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 Frame	Cycle 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

Title	Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
Description	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).
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

47. Secondary Outcome

Title	Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
Description	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 Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Treatment-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 Title	Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD		Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
Arm/Group Description	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.		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 + AVD		Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/59 (0%)
Serious Adverse Events
	Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD		Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		24/59 (40.7%)
Blood and lymphatic system disorders
Febrile neutropenia	1/8 (12.5%)	1	10/59 (16.9%)	18
Neutropenia	0/8 (0%)	0	3/59 (5.1%)	3
Anaemia	0/8 (0%)	0	1/59 (1.7%)	1
Cardiac disorders
Intracardiac thrombus	0/8 (0%)	0	1/59 (1.7%)	1
Gastrointestinal disorders
Vomiting	0/8 (0%)	0	3/59 (5.1%)	4
Constipation	0/8 (0%)	0	2/59 (3.4%)	2
Gastrointestinal disorder	0/8 (0%)	0	2/59 (3.4%)	2
Abdominal pain	0/8 (0%)	0	1/59 (1.7%)	2
Nausea	0/8 (0%)	0	2/59 (3.4%)	2
Abdominal pain upper	0/8 (0%)	0	1/59 (1.7%)	1
Colitis	0/8 (0%)	0	1/59 (1.7%)	1
Ileus	0/8 (0%)	0	1/59 (1.7%)	2
General disorders
Pyrexia	0/8 (0%)	0	2/59 (3.4%)	2
Mucosal inflammation	0/8 (0%)	0	1/59 (1.7%)	1
Infections and infestations
Sepsis	0/8 (0%)	0	2/59 (3.4%)	2
Bacteraemia	0/8 (0%)	0	1/59 (1.7%)	1
Device related infection	0/8 (0%)	0	1/59 (1.7%)	1
Herpes zoster	0/8 (0%)	0	1/59 (1.7%)	1
Lip infection	0/8 (0%)	0	1/59 (1.7%)	1
Pneumonia	0/8 (0%)	0	1/59 (1.7%)	1
Skin infection	0/8 (0%)	0	1/59 (1.7%)	1
Investigations
Neutrophil count decreased	0/8 (0%)	0	1/59 (1.7%)	7
White blood cell count decreased	0/8 (0%)	0	1/59 (1.7%)	1
Metabolism and nutrition disorders
Dehydration	0/8 (0%)	0	1/59 (1.7%)	1
Hyperuricaemia	0/8 (0%)	0	1/59 (1.7%)	1
Nervous system disorders
Peripheral motor neuropathy	0/8 (0%)	0	1/59 (1.7%)	1
Posterior reversible encephalopathy syndrome	0/8 (0%)	0	1/59 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/8 (0%)	0	1/59 (1.7%)	1
Dyspnoea	0/8 (0%)	0	1/59 (1.7%)	1
Hypoxia	0/8 (0%)	0	1/59 (1.7%)	1
Pneumothorax	0/8 (0%)	0	1/59 (1.7%)	2
Pulmonary embolism	0/8 (0%)	0	1/59 (1.7%)	1
Vascular disorders
Venous thrombosis	0/8 (0%)	0	1/59 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD		Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		59/59 (100%)
Blood and lymphatic system disorders
Neutropenia	5/8 (62.5%)	40	33/59 (55.9%)	210
Anaemia	1/8 (12.5%)	1	13/59 (22%)	28
Leukopenia	1/8 (12.5%)	2	6/59 (10.2%)	9
Thrombocytopenia	1/8 (12.5%)	1	2/59 (3.4%)	2
Cardiac disorders
Sinus tachycardia	0/8 (0%)	0	5/59 (8.5%)	6
Palpitations	1/8 (12.5%)	1	1/59 (1.7%)	1
Eye disorders
Conjunctival hyperaemia	1/8 (12.5%)	1	2/59 (3.4%)	2
Eyelid oedema	1/8 (12.5%)	1	1/59 (1.7%)	1
Gastrointestinal disorders
Vomiting	8/8 (100%)	65	50/59 (84.7%)	204
Nausea	8/8 (100%)	24	44/59 (74.6%)	131
Abdominal pain	2/8 (25%)	2	23/59 (39%)	42
Stomatitis	4/8 (50%)	6	22/59 (37.3%)	30
Constipation	4/8 (50%)	6	21/59 (35.6%)	37
Diarrhoea	4/8 (50%)	5	14/59 (23.7%)	25
Abdominal pain upper	3/8 (37.5%)	5	10/59 (16.9%)	12
Oral pain	1/8 (12.5%)	1	8/59 (13.6%)	8
Odynophagia	2/8 (25%)	2	5/59 (8.5%)	6
Dyspepsia	1/8 (12.5%)	1	3/59 (5.1%)	3
Toothache	0/8 (0%)	0	3/59 (5.1%)	3
Mouth ulceration	1/8 (12.5%)	1	2/59 (3.4%)	2
General disorders
Pyrexia	4/8 (50%)	5	24/59 (40.7%)	32
Fatigue	3/8 (37.5%)	6	12/59 (20.3%)	18
Asthenia	5/8 (62.5%)	7	8/59 (13.6%)	13
Pain	0/8 (0%)	0	6/59 (10.2%)	7
Catheter site pain	1/8 (12.5%)	1	4/59 (6.8%)	4
Chills	1/8 (12.5%)	1	3/59 (5.1%)	4
Influenza like illness	0/8 (0%)	0	3/59 (5.1%)	4
Non-cardiac chest pain	1/8 (12.5%)	1	1/59 (1.7%)	1
Hepatobiliary disorders
Hepatotoxicity	1/8 (12.5%)	1	1/59 (1.7%)	1
Infections and infestations
Rhinitis	3/8 (37.5%)	4	10/59 (16.9%)	13
Conjunctivitis	2/8 (25%)	6	6/59 (10.2%)	10
Upper respiratory tract infection	1/8 (12.5%)	1	6/59 (10.2%)	6
Oral herpes	1/8 (12.5%)	2	5/59 (8.5%)	6
Pharyngitis	1/8 (12.5%)	1	4/59 (6.8%)	4
Influenza	1/8 (12.5%)	1	2/59 (3.4%)	2
Injury, poisoning and procedural complications
Nail avulsion	1/8 (12.5%)	1	1/59 (1.7%)	1
Investigations
White blood cell count decreased	5/8 (62.5%)	21	25/59 (42.4%)	115
Neutrophil count decreased	4/8 (50%)	18	22/59 (37.3%)	96
Weight decreased	1/8 (12.5%)	1	13/59 (22%)	24
Lymphocyte count decreased	0/8 (0%)	0	7/59 (11.9%)	32
Polymerase chain reaction positive	1/8 (12.5%)	1	4/59 (6.8%)	7
Alanine aminotransferase increased	2/8 (25%)	2	3/59 (5.1%)	3
Aspartate aminotransferase increased	1/8 (12.5%)	7	2/59 (3.4%)	8
Gamma-glutamyltransferase increased	1/8 (12.5%)	1	2/59 (3.4%)	2
Metabolism and nutrition disorders
Decreased appetite	2/8 (25%)	2	14/59 (23.7%)	23
Dehydration	0/8 (0%)	0	5/59 (8.5%)	5
Acidosis	1/8 (12.5%)	1	1/59 (1.7%)	1
Hyperuricaemia	1/8 (12.5%)	1	1/59 (1.7%)	1
Hypoalbuminaemia	1/8 (12.5%)	1	1/59 (1.7%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/8 (25%)	6	14/59 (23.7%)	22
Arthralgia	1/8 (12.5%)	1	9/59 (15.3%)	13
Bone pain	0/8 (0%)	0	8/59 (13.6%)	19
Pain in extremity	2/8 (25%)	3	8/59 (13.6%)	9
Myalgia	1/8 (12.5%)	1	6/59 (10.2%)	6
Pain in jaw	0/8 (0%)	0	6/59 (10.2%)	7
Groin pain	1/8 (12.5%)	1	3/59 (5.1%)	4
Muscular weakness	0/8 (0%)	0	3/59 (5.1%)	3
Musculoskeletal pain	2/8 (25%)	2	3/59 (5.1%)	3
Spinal pain	2/8 (25%)	2	3/59 (5.1%)	3
Nervous system disorders
Headache	5/8 (62.5%)	7	19/59 (32.2%)	27
Dizziness	1/8 (12.5%)	1	7/59 (11.9%)	8
Peripheral sensory neuropathy	2/8 (25%)	4	5/59 (8.5%)	8
Paraesthesia	0/8 (0%)	0	3/59 (5.1%)	3
Peripheral motor neuropathy	0/8 (0%)	0	3/59 (5.1%)	3
Dysgeusia	1/8 (12.5%)	1	2/59 (3.4%)	2
Psychiatric disorders
Anxiety	1/8 (12.5%)	1	5/59 (8.5%)	5
Insomnia	1/8 (12.5%)	2	4/59 (6.8%)	5
Reproductive system and breast disorders
Pelvic pain	1/8 (12.5%)	1	1/59 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	3/8 (37.5%)	3	13/59 (22%)	14
Cough	1/8 (12.5%)	1	9/59 (15.3%)	10
Nasal congestion	2/8 (25%)	4	7/59 (11.9%)	9
Rhinitis allergic	0/8 (0%)	0	3/59 (5.1%)	4
Pharyngeal erythema	1/8 (12.5%)	1	2/59 (3.4%)	2
Laryngeal pain	1/8 (12.5%)	1	1/59 (1.7%)	1
Dyspnoea	0/8 (0%)	0	5/59 (8.5%)	6
Skin and subcutaneous tissue disorders
Alopecia	0/8 (0%)	0	11/59 (18.6%)	13
Pruritus	0/8 (0%)	0	7/59 (11.9%)	8
Rash maculo-papular	2/8 (25%)	2	6/59 (10.2%)	8
Dermatitis contact	1/8 (12.5%)	1	4/59 (6.8%)	4
Dry skin	1/8 (12.5%)	1	3/59 (5.1%)	3
Erythema	2/8 (25%)	2	3/59 (5.1%)	3
Papule	1/8 (12.5%)	1	3/59 (5.1%)	3
Rash	0/8 (0%)	0	3/59 (5.1%)	3
Urticaria	0/8 (0%)	0	3/59 (5.1%)	3
Dermatitis acneiform	1/8 (12.5%)	1	2/59 (3.4%)	3
Vascular disorders
Hyperaemia	2/8 (25%)	2	2/59 (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.