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CompletedNCT01492088Updated May 30, 2024Results posted

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

A Phase 1/2 interventional study of Brentuximab vedotin in Relapsed or Refractory Hodgkin Lymphoma and Relapsed or Refractory Anaplastic Large-cell Lymphoma, sponsored by Millennium Pharmaceuticals, Inc.. Completed at 18 sites in 8 countries. Open to participants aged 2 Years to 18 Years. Per ClinicalTrials.gov, last updated 2024-05-30.

Sponsored by Millennium Pharmaceuticals, Inc. · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
36
Allocation
Non-randomized
Ages
2 Years to 18 Years
Sex
All
01

Study summary

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

Read the detailed description

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

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

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

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

02

Conditions studied

  • Relapsed or Refractory Hodgkin Lymphoma
  • Relapsed or Refractory Anaplastic Large-cell Lymphoma

Keywords

  • Pediatric
  • Lymphoma
  • Hodgkin
  • Anaplastic Large-cell
  • Relapsed
  • Refractory
  • Drug therapy
03

Who can participate

Ages eligible
2 Years to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Male or female participants aged 2 to \<18 years (5 to \<18 years for Hodgkin lymphoma [HL])
  • Diagnosis of systemic anaplastic large-cell lymphoma (sALCL), or HL for which standard, curative, life-prolonging, or palliative treatment does not exist or is no longer effective
  • Participants with sALCL must have documented anaplastic lymphoma kinase (ALK) status and must be beyond first remission or refractory to front-line chemotherapy
  • Participants diagnosed with any relapsed or refractory CD30+ hematologic malignancy (e.g., primary mediastinal B-cell lymphoma) may be included in phase 1 of the study
  • Participants with HL must be in their second of later relapse, have failed systemic chemotherapy either as induction therapy for advanced stage disease or salvage therapy, and were ineligible for, refused, or previously received a stem cell transplant
  • Performance score ≥ 60 from Lansky Play Performance Scale if ≤16 years
  • Negative pregnancy test
  • Fertile Participants must use 2 effective methods of contraception prior to and through 6 months after the last dose of the study drug

Exclusion criteria

Exclusion Criteria:

  • Current diagnosis of primary cutaneous ALCL (those with systemic ALCL are eligible)
  • Received an allogeneic stem cell transplant \<3 months prior to the first dose of study medication, or presence of polymerase chain reaction (PCR)-detectable cytomegalovirus (CMV) in any post-allogeneic transplant participant
  • Receiving immunosuppressive therapy
  • Receiving systemic therapy for chronic graft-versus-host disease (topical therapy is allowed)
  • Previous treatment with any anti-CD30 antibody
  • Therapeutic monoclonal antibody use within the longer of 6 weeks or 5 plasma half-lives
  • Systemic cardiac disease that would, in the opinion of the investigator or medical monitor, interfere with assessment of efficacy or safety of the drug
  • History of another primary malignancy not in remission for at least 3 years (the following are exempt from the 3-year limit: nonmelanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)
  • Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML
  • History of cirrhosis
  • Active systemic viral, bacterial, or fungal infection requiring antimicrobial, antiviral therapy or antifungal therapy within 2 weeks prior to the first dose of study drug (routine antimicrobial prophylaxis is acceptable)
  • Concurrent therapy with other anti-neoplastic or experimental agents
  • Systemic corticosteroid therapy \<7 days prior to first dose of the study medication
  • Any serious underlying medical condition that, in the opinion of the investigator or medical monitor, would impair their ability to receive or tolerate the planned treatment
  • Known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation
  • Received nitrogen mustard agents, melphalan, or BCNU therapy within 6 weeks prior to the first study dose
  • Prior autologous hematopoietic stem cell infusion \<4 weeks prior to first study dose
  • Grade 2 or greater unresolved toxicity from prior antineoplastic therapy
  • Grade 2 or greater peripheral neuropathy
  • Female participants who are both lactating and breastfeeding, or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug
  • Received local palliative radiation therapy \<14 days prior to the first dose of study medication
  • Received radiation therapy to more than 25% of the bone marrow-containing spaces \< 84 days prior to first dose of study medication
  • Received a strong or listed moderate inhibitor of CYP3A4 \<2 weeks prior to first study dose
  • Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    Brentuximab vedotin: Phase 1

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

    Drug: Brentuximab vedotin

  • Experimental
    Brentuximab vedotin: Phase 2

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

    Drug: Brentuximab vedotin

Interventions

  • DrugBrentuximab vedotin

    Brentuximab vedotin IV infusion

    Also known as: SGN-35, ADCETRIS

05

What researchers measure

Primary outcomes

  1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1)

    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

    Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)

  2. Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1)

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

    Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)

  3. Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1)

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

    Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)

  4. Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1)

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

    Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

  5. Serum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1)

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

    Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

  6. Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1)

    Blood samples were collected and tested for MMAE plasma concentrations.

    Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

  7. Overall Response Rate (ORR) (Phase 1 and 2)

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

    Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months)

Secondary outcomes

  1. Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2)

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

    Time frame: Baseline up to EOT (Up to 15 months)

  2. Overall Response Rate (ORR) (Phase 1)

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

    Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)

  3. Time to Progression (TTP) (Phase 1 and 2)

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

    Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)

  4. Time to Response (Phase 1 and 2)

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

    Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)

  5. Duration of Response (DOR) (Phase 1 and 2)

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

    Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)

  6. Event Free Survival (EFS) (Phase 1 and 2)

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

    Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)

  7. Progression Free Survival (PFS) (Phase 1 and 2)

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

    Time frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)

  8. Overall Survival (OS) (Phase 1 and 2)

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

    Time frame: Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrolment of the last participant (Up to 72 months)

  9. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2)

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

    Time frame: From the first dose through 30 days after the last dose of study medication (up to 15 months)

  10. Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2)

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

    Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)

  11. Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2)

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

    Time frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months)

  12. Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2)

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

    Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

  13. Serum Concentration of Total Antibodies (Conjugated and Unconjugated)

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

    Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

  14. Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2)

    Blood samples were collected and tested for MMAE plasma concentrations.

    Time frame: Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

06

Results

Posted May 15, 2017

Participant flow

Participants took part in the study at 12 investigative sites in United States, France, Germany, Netherlands, United Kingdom, Italy, Spain and Mexico from 16-April-2012 to 12-April-2018.

Participant flow — Overall Study
MilestoneBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Started31617
Completed023
Not completed31414
Withdrew: Withdrawal by patient020
Withdrew: Death162
Withdrew: Completed post treatment followup (ptfu)201
Withdrew: Alive at last follow-up0611

Outcome measures

PrimaryNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

Time frame:
From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1)
ParticipantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
TEAE39
SAE04
PrimaryNumber of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1)

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

Time frame:
From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1)
ParticipantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
Gamma-glutamyltransferase increased01
Transaminases increased01
Lymphocyte count decreased11
Neutrophil count decreased01
Blood bicarbonate decreased01
Weight decreased01
Hypocalaemia02
Hyperuricaemia01
PrimaryNumber of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1)

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

Time frame:
From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1)
ParticipantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1)00
PrimaryAntibody-drug Conjugate (ADC) Serum Concentrations (Phase 1)

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

Time frame:
Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

No measurements were reported for this outcome.

PrimarySerum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1)

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

Time frame:
Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

No measurements were reported for this outcome.

PrimaryMonomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1)

Blood samples were collected and tested for MMAE plasma concentrations.

Time frame:
Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

No measurements were reported for this outcome.

PrimaryOverall Response Rate (ORR) (Phase 1 and 2)

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

Time frame:
Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months)
Reported as:
Number · percentage of participants
Overall Response Rate (ORR) (Phase 1 and 2)
percentage of participantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Overall Response Rate (ORR) (Phase 1 and 2)0 (0 to 71)47 (21 to 73)53 (28 to 77)
SecondaryNumber of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2)

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

Time frame:
Baseline up to EOT (Up to 15 months)
Reported as:
Count of participants · Participants
Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2)
ParticipantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
ATA status: Transiently positive147
ATA status: Persistently positive020
nATA status: Positive054
SecondaryOverall Response Rate (ORR) (Phase 1)

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

Time frame:
Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)
Reported as:
Number · percentage of participants
Overall Response Rate (ORR) (Phase 1)
percentage of participantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
Overall Response Rate (ORR) (Phase 1)0 (0 to 71)63 (24 to 91)
SecondaryTime to Progression (TTP) (Phase 1 and 2)

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

Time frame:
Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)
Reported as:
Median · months
Time to Progression (TTP) (Phase 1 and 2)
monthsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Time to Progression (TTP) (Phase 1 and 2)2.7 (1.4 to 2.8)4.8 (1.2 to NA)6.2 (2.8 to NA)
SecondaryTime to Response (Phase 1 and 2)

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

Time frame:
Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)
Reported as:
Median · months
Time to Response (Phase 1 and 2)
monthsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Time to Response (Phase 1 and 2)NA (NA to NA)2.7 (1.3 to NA)1.5 (1.2 to NA)
SecondaryDuration of Response (DOR) (Phase 1 and 2)

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

Time frame:
Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)
Reported as:
Median · months
Duration of Response (DOR) (Phase 1 and 2)
monthsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Duration of Response (DOR) (Phase 1 and 2)—NA (2.2 to NA)30.3 (3.4 to 30.3)
SecondaryEvent Free Survival (EFS) (Phase 1 and 2)

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

Time frame:
Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)
Reported as:
Median · months
Event Free Survival (EFS) (Phase 1 and 2)
monthsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Event Free Survival (EFS) (Phase 1 and 2)2.7 (1.4 to 2.8)2.1 (1.2 to 4.8)4.8 (2.8 to 7.4)
SecondaryProgression Free Survival (PFS) (Phase 1 and 2)

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

Time frame:
Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)
Reported as:
Median · months
Progression Free Survival (PFS) (Phase 1 and 2)
monthsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Progression Free Survival (PFS) (Phase 1 and 2)2.7 (1.4 to 2.8)3.8 (1.2 to NA)6.2 (2.8 to 31.5)
SecondaryOverall Survival (OS) (Phase 1 and 2)

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

Time frame:
Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrolment of the last participant (Up to 72 months)
Reported as:
Median · months
Overall Survival (OS) (Phase 1 and 2)
monthsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Overall Survival (OS) (Phase 1 and 2)NA (NA to NA)NA (NA to NA)NA (NA to NA)
SecondaryNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2)

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

Time frame:
From the first dose through 30 days after the last dose of study medication (up to 15 months)
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2)
ParticipantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
TEAEs31617
SAEs071
SecondaryNumber of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2)

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

Time frame:
From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2)
ParticipantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Gamma-glutamyltransferase increased020
Alanine aminotransferase increased010
Aspartate aminotransferase increased010
Transaminases increased010
Lymphocyte count decreased102
Neutrophil count decreased002
White blood cell count decreased001
Blood bicarbonate decreased010
Weight decreased001
C-reactive protein increased010
Blood alkaline phosphatase increased010
SecondaryNumber of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2)

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

Time frame:
From the first dose through 30 days after the last dose of study medication (Up to 15 months)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2)
ParticipantsBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2)000
SecondaryAntibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2)

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

Time frame:
Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Reported as:
Mean · ug/mL
Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2)
ug/mLBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
Cycle 1 Day 1, Pre-Dose—NA ± NA
Cycle 1 Day 1, 5 Minutes Post-Dose23.1 ± 3.4631.8 ± 12.4
Cycle 1 Day 2, 24 Hours Post-Dose9.50 ± 1.7313.0 ± 5.34
Cycle 1 Day 3, 48 Hours Post-Dose5.67 ± 0.92412.0 ± 16.3
Cycle 1 Day 5, 96 Hours Post-Dose3.50 ± 1.418.68 ± 13.4
Cycle 1 Day 14, 312 Hours Post-Dose0.844 ± 0.3092.19 ± 3.44
Cycle 2 Day 1, Pre-Dose0.149 ± 0.1280.395 ± 0.322
Cycle 2 Day 1, 5-minutes Post-Dose25.3 ± 7.5632.9 ± 9.80
Cycle 2 Day 2, 24 Hours Post-Dose8.80 ± 6.1910.4 ± 8.05
Cycle 2 Day 3, 48 Hours Post-Dose3.70 ± 1.9511.4 ± 16.8
Cycle 2 Day 5, 96 Hours Post-Dose2.04 ± 1.269.61 ± 17.9
Cycle 3 Day 1, Pre-Dose0.116 ± 0.1630.491 ± 0.387
Cycle 3 Day 1, 5 minutes Post-Dose23.9 ± 2.8331.3 ± 9.79
Cycle 4 Day 1, Pre-dose0.218 ± 0.2710.691 ± 0.492
Cycle 4 Day 1, 5 minutes Post-Dose22.9 ± 4.6030.0 ± 12.2
Cycle 5 Day 1, Pre-Dose0.264 ± 0.3210.845 ± 0.564
Cycle 5 Day 1, 5 minutes Post-Dose22.5 ± 3.3230.6 ± 15.1
Cycle 6 Day 1, Pre-Dose0.312 ± 0.3511.06 ± 0.699
Cycle 6 Day 1, 5 minutes Post-Dose20.3 ± 4.3833.2 ± 16.1
Cycle 7 Day 1, Pre-Dose0.327 ± 0.3371.04 ± 0.618
Cycle 7 Day 1, 5 minutes Post-Dose17.9 ± 2.4032.3 ± 15.4
Cycle 8 Day 1, Pre-Dose—1.25 ± 0.565
Cycle 8 Day 1, 5 minutes Post-Dose—35.2 ± 10.5
Cycle 8 Day 2, 24 Hours Post-Dose—14.0 ± 4.55
Cycle 8 Day 3, 48 Hours Post-Dose—9.53 ± 2.96
Cycle 8 Day 5, 96 Hours Post-Dose—6.44 ± 2.35
Cycle 8 Day 14, 312 Hours Post-Dose—3.30 ± 4.63
Cycle 9 Day 1, Pre-Dose—4.37 ± 11.7
Cycle 9 Day 1, 5 Minutes Post-Dose—29.6 ± 11.3
Cycle 10 Day 1, Pre-Dose—1.20 ± 0.455
Cycle 10 Day 1, 5 minutes Post-Dose—35.7 ± 9.50
Cycle 11 Day 1, Pre-Dose—1.84 ± 1.57
Cycle 11 Day 1, 5 minutes Post-Dose—35.7 ± 10.8
Cycle 12 Day 1, Pre-Dose—1.47 ± 0.665
Cycle 12 Day 1, 5 minutes Post-Dose—40.0 ± 10.4
Cycle 13 Day 1, Pre-Dose—6.28 ± 11.5
Cycle 13 Day 1, 5 minutes Post-Dose—33.3 ± 16.1
Cycle 14 Day 1, Pre-Dose—1.60 ± 0.600
Cycle 14 Day 1, 5 minutes Post-Dose—37.0 ± 7.92
Cycle 15 Day 1, Pre-Dose—1.48 ± 0.542
Cycle 15 Day 1, 5 minutes Post-Dose—40.3 ± 10.6
Cycle 16 Day 1, Pre-Dose—1.52 ± 0.361
Cycle 16 Day 1, 5 minutes Post-Dose—41.5 ± 4.70
SecondarySerum Concentration of Total Antibodies (Conjugated and Unconjugated)

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

Time frame:
Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Reported as:
Mean · ug/mL
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
ug/mLBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
Cycle 1 Day 1, Pre-DoseNA ± NANA ± NA
Cycle 1 Day 1, 5 Minutes Post-Dose26.3 ± 2.2934.7 ± 13.4
Cycle 1 Day 2, 24 Hours Post-Dose16.7 ± 1.5025.0 ± 9.59
Cycle 1 Day 3, 48 Hours Post-Dose12.7 ± 3.1318.5 ± 7.57
Cycle 1 Day 5, 96 Hours Post-Dose8.63 ± 5.1111.8 ± 5.02
Cycle 1 Day 14, 312 Hours Post-Dose2.23 ± 0.8333.50 ± 1.70
Cycle 2 Day 1, Pre-Dose0.470 ± 0.4591.16 ± 0.825
Cycle 2 Day 1, 5-minutes Post-Dose26.9 ± 7.9835.6 ± 12.0
Cycle 2 Day 2, 24 Hours Post-Dose17.1 ± 10.417.2 ± 7.93
Cycle 2 Day 3, 48 Hours Post-Dose9.60 ± 5.3916.0 ± 6.73
Cycle 2 Day 3, 96 Hours Post-Dose6.43 ± 3.6910.2 ± 5.16
Cycle 3 Day 1, Pre-Dose0.415 ± 0.5861.62 ± 1.07
Cycle 3 Day 1, 5 minutes Post-Dose30.0 ± 5.8738.2 ± 13.1
Cycle 4 Day 1, Pre-dose0.875 ± 1.031.95 ± 1.26
Cycle 4 Day 1, 5 minutes Post-Dose29.6 ± 8.1337.1 ± 15.6
Cycle 5 Day 1, Pre-Dose0.844 ± 0.9282.45 ± 1.68
Cycle 5 Day 1, 5 minutes Post-Dose29.4 ± 3.0438.0 ± 18.8
Cycle 6 Day 1, Pre-Dose1.05 ± 1.202.99 ± 1.81
Cycle 6 Day 1, 5 minutes Post-Dose29.4 ± 5.3739.8 ± 19.8
Cycle 7 Day 1, Pre-Dose0.995 ± 0.9982.92 ± 1.62
Cycle 7 Day 1, 5 minutes Post-Dose24.0 ± 2.6941.0 ± 21.2
Cycle 8 Day 1, Pre-Dose—3.29 ± 1.14
Cycle 8 Day 1, 5 minutes Post-Dose—41.4 ± 9.47
Cycle 8 Day 2, 24 Hours Post-Dose—28.2 ± 6.38
Cycle 8 Day 3, 48 Hours Post-Dose—22.9 ± 5.67
Cycle 8 Day 5, 96 Hours Post-Dose—17.3 ± 4.93
Cycle 8 Day 14, 312 Hours Post-Dose—5.74 ± 2.02
Cycle 9 Day 1, Pre-Dose—6.30 ± 12.0
Cycle 9 Day 1, 5 Minutes Post-Dose—35.1 ± 11.3
Cycle 10 Day 1, Pre-Dose—3.48 ± 1.13
Cycle 10 Day 1, 5 minutes Post-Dose—41.4 ± 8.63
Cycle 11 Day 1, Pre-Dose—3.96 ± 2.24
Cycle 11 Day 1, 5 minutes Post-Dose—42.8 ± 8.85
Cycle 12 Day 1, Pre-Dose—3.47 ± 1.28
Cycle 12 Day 1, 5 minutes Post-Dose—44.8 ± 10.3
Cycle 13 Day 1, Pre-Dose—11.3 ± 17.1
Cycle 13 Day 1, 5 minutes Post-DoseNA ± NA40.3 ± 19.2
Cycle 14 Day 1, Pre-Dose—3.97 ± 1.14
Cycle 14 Day 1, 5 minutes Post-Dose—44.5 ± 7.05
Cycle 15 Day 1, Pre-Dose—4.02 ± 1.40
Cycle 15 Day 1, 5 minutes Post-Dose—49.7 ± 6.88
Cycle 16 Day 1, Pre-Dose—4.60 ± 1.67
Cycle 16 Day 1, 5 minutes Post-Dose—49.7 ± 7.61
SecondaryMonomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2)

Blood samples were collected and tested for MMAE plasma concentrations.

Time frame:
Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose
Reported as:
Mean · ng/mL
Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2)
ng/mLBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1
Cycle 1 Day 1, Pre-DoseNA ± NANA ± NA
Cycle 1 Day 1, 5 Minutes Post-Dose0.416 ± 0.4800.368 ± 0.309
Cycle 1 Day 2, 24 Hours Post-Dose4.63 ± 3.204.88 ± 3.55
Cycle 1 Day 3, 48 Hours Post-Dose4.20 ± 1.955.36 ± 3.72
Cycle 1 Day 5, 96 Hours Post-Dose2.80 ± 0.3004.43 ± 3.04
Cycle 1 Day 14, 312 Hours Post-Dose0.196 ± 0.06410.530 ± 0.552
Cycle 2 Day 1, Pre-Dose0.0647 ± 0.03580.0739 ± 0.0640
Cycle 2 Day 1, 5-minutes Post-Dose0.556 ± 0.5620.478 ± 0.461
Cycle 2 Day 2, 24 Hours Post-Dose5.63 ± 5.723.71 ± 3.94
Cycle 2 Day 3, 48 Hours Post-Dose4.60 ± 3.703.86 ± 3.18
Cycle 2 Day 5, 96 Hours Post-Dose2.60 ± 1.042.70 ± 1.69
Cycle 3 Day 1, Pre-Dose0.0250 ± 0.03540.0650 ± 0.0590
Cycle 3 Day 1, 5 minutes Post-Dose0.216 ± 0.03610.514 ± 0.684
Cycle 4 Day 1, Pre-dose0.0565 ± 0.004950.0866 ± 0.0784
Cycle 4 Day 1, 5 minutes Post-Dose0.234 ± 0.07420.376 ± 0.449
Cycle 5 Day 1, Pre-Dose0.0820 ± NA0.0862 ± 0.0729
Cycle 5 Day 1, 5 minutes Post-Dose0.334 ± 0.09550.301 ± 0.248
Cycle 6 Day 1, Pre-Dose0.0680 ± 0.01560.0841 ± 0.0632
Cycle 6 Day 1, 5 minutes Post-Dose0.247 ± 0.007070.450 ± 0.663
Cycle 7 Day 1, Pre-Dose0.104 ± 0.03890.0830 ± 0.0578
Cycle 7 Day 1, 5 minutes Post-Dose0.326 ± 0.03610.310 ± 0.282
Cycle 8 Day 1, Pre-Dose—0.101 ± 0.934
Cycle 8 Day 1, 5 minutes Post-Dose—0.295 ± 0.151
Cycle 8 Day 2, 24 Hours Post-Dose—1.96 ± 1.31
Cycle 8 Day 3, 48 Hours Post-Dose—1.91 ± 1.29
Cycle 8 Day 5, 96 Hours Post-Dose—2.00 ± 1.05
Cycle 8 Day 14, 312 Hours Post-Dose—0.325 ± 0.214
Cycle 9 Day 1, Pre-Dose—0.0819 ± 0.0496
Cycle 9 Day 1, 5 Minutes Post-Dose—0.218 ± 0.128
Cycle 10 Day 1, Pre-Dose—0.727 ± 0.0517
Cycle 10 Day 1, 5 minutes Post-Dose—0.204 ± 0.0982
Cycle 11 Day 1, Pre-Dose—0.0763 ± 0.0368
Cycle 11 Day 1, 5 minutes Post-Dose—0.255 ± 0.133
Cycle 12 Day 1, Pre-Dose—0.105 ± 0.0983
Cycle 12 Day 1, 5 minutes Post-Dose—0.252 ± 0.116
Cycle 13 Day 1, Pre-Dose—0.110 ± 0.0629
Cycle 13 Day 1, 5 minutes Post-Dose—0.244 ± 0.130
Cycle 14 Day 1, Pre-Dose—0.109 ± 0.0529
Cycle 14 Day 1, 5 minutes Post-Dose—0.320 ± 0.138
Cycle 15 Day 1, Pre-Dose—0.0843 ± 0.0548
Cycle 15 Day 1, 5 minutes Post-Dose—0.404 ± 0.192
Cycle 16 Day 1, Pre-Dose—0.139 ± 0.0926
Cycle 16 Day 1, 5 minutes Post-Dose—0.381 ± 0.277

Adverse events

Collected over From the first dose through 30 days after the last dose of study medication (Up to 15 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Brentuximab Vedotin 1.4 mg/kg: Phase 11/3 (33.3%)0/3 (0%)3/3 (100%)
Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only6/16 (37.5%)7/16 (43.8%)16/16 (100%)
Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only2/17 (11.8%)1/17 (5.9%)17/17 (100%)
Most frequent serious events
Most frequent serious events
EventBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
HepatotoxicityHepatobiliary disorders0/31/160/17
Febrile neutropeniaBlood and lymphatic system disorders0/31/160/17
PneumoniaInfections and infestations0/31/160/17
PyrexiaGeneral disorders0/31/161/17
VomitingGastrointestinal disorders0/31/160/17
Anaphylactic reactionImmune system disorders0/31/160/17
Supraventricular tachycardiaCardiac disorders0/31/160/17
Cardiac arrestCardiac disorders0/31/160/17
MyalgiaGeneral disorders0/31/160/17
Most frequent other events
Showing 10 of 107
Most frequent other events
EventBrentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only
NauseaGastrointestinal disorders2/37/164/17
PyrexiaGeneral disorders1/38/167/17
Abdominal pain upperGastrointestinal disorders1/32/161/17
Abdominal painGastrointestinal disorders1/32/160/17
Upper respiratory tract infectionInfections and infestations1/30/160/17
ParaesthesiaNervous system disorders1/35/161/17
DysgeusiaNervous system disorders1/30/160/17
ArthralgiaMusculoskeletal and connective tissue disorders1/31/160/17
Drug eruptionSkin and subcutaneous tissue disorders1/30/160/17
Lymphocyte count decreasedInvestigations1/30/162/17

Baseline characteristics

Safety population is defined as participants who received at least 1 dose of study drug.

Age, Continuous
Age, Continuous(years)Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
Mean14.7 ± 1.1514.5 ± 2.6811.5 ± 3.1813.1 ± 3.19
Sex: Female, Male
Sex: Female, Male(Participants)Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
Female17311
Male291425
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
Hispanic or Latino0044
Not Hispanic or Latino3141229
Unknown or Not Reported0213
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
White2131631
Asian1012
Other0202
Not Reported0101
Region of Enrollment
Region of Enrollment(Participants)Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
United States2114
France0202
Germany0415
Netherlands0123
United Kingdom0123
Italy17614
Spain0044
Mexico0011
Height
Height(cm)Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
Mean167.17 ± 10.865165.31 ± 14.350149.54 ± 17.783158.02 ± 17.493
Weight
Weight(kg)Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
Mean53.10 ± 9.92457.85 ± 17.53942.16 ± 15.16250.04 ± 17.361
Body Surface Area
Body Surface Area(m^2)Brentuximab Vedotin 1.4 mg/kg: Phase 1Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL OnlyBrentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL OnlyTotal
Mean1.562 ± 0.09671.617 ± 0.29381.313 ± 0.31031.469 ± 0.3228
07

Study locations

18 sites
  • Aurora, Colorado, United States
  • Kansas City, Missouri, United States
  • New York, New York, United States
  • Houston, Texas, United States
  • Bordeaux Cedex, France
  • Lyon, France
  • Paris Cedex 12, France
  • Berlin, Germany
  • Frankfurt, Germany
  • Giessen, Germany
  • Halle, Germany
  • Munster, Germany
  • Padova, Italy
  • Roma, Italy
  • Mexico Df, Mexico
  • Rotterdam, Netherlands
  • Barcelona, Spain
  • London, United Kingdom
08

References and documents

Publications

  • Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22. PubMed 17242396 ↗
  • Suri A, Mould DR, Song G, Kinley J, Venkatakrishnan K. Population Pharmacokinetics of Brentuximab Vedotin in Adult and Pediatric Patients With Relapsed/Refractory Hematologic Malignancies: Model-Informed Hypothesis Generation for Pediatric Dosing Regimens. J Clin Pharmacol. 2020 Dec;60(12):1585-1597. doi: 10.1002/jcph.1682. Epub 2020 Jun 28. PubMed 32596842 ↗
  • Locatelli F, Mauz-Koerholz C, Neville K, Llort A, Beishuizen A, Daw S, Pillon M, Aladjidi N, Klingebiel T, Landman-Parker J, Medina-Sanson A, August K, Sachs J, Hoffman K, Kinley J, Song S, Song G, Zhang S, Suri A, Gore L. Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study. Lancet Haematol. 2018 Oct;5(10):e450-e461. doi: 10.1016/S2352-3026(18)30153-4. PubMed 30290902 ↗

Study documents

  • Study protocol · Jun 12, 2014
  • Statistical analysis plan · Dec 1, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT01492088
Lead sponsor
Millennium Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Dec 14, 2011
Start date
Apr 16, 2012
Primary completion
Oct 12, 2016
Completion
Apr 12, 2018
Results posted
May 15, 2017
Last update
May 30, 2024

Study contacts

Medical Monitor
study director · Millennium Pharmaceuticals, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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