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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 1/2 Study of Brentuximab Vedotin (SGN-35) in Pediatric Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma

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

Detailed Summary:

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.


Sponsor: Millennium Pharmaceuticals, Inc.

Current Primary Outcome:

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) [ Time Frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months) ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
  • Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) [ Time Frame: From the first dose through 30 days after the last dose of study medication (Up to 15 months) ]
    Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
  • Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1) [ Time Frame: From the first dose through 30 days after t

    Original Primary Outcome:

    • Adverse events, serious adverse events, assessments of clinical and laboratory values, and vital sign measurements (phase 1) [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 12 months ]
    • Plasma concentrations of brentuximab vedotin, total therapeutic antibody, and monomethyl auristatin E (MMAE) (phase 1) [ Time Frame: All (21 day) Cycles: Day 1; Cycle 1: Days 2, 3, 5, 14; Cycle 2: Days 2 (phase 1 only), 3, 5; Cycle 8: Days 2, 3, 5, 14 ]
      Pharmacokinetics of brentuximab vedotin
    • Number of patients with overall response as determined by an IRF using PET, CT and, clinical assessment according to IWG revised response criteria (phase 2) [ Time Frame: PET: At Screening, Cycles 2 and 7. No additional scans needed after Cycle 7 unless clinically indicated. CT: Screening, Cycle 2, 4, 7, 10, 13, 16 and end of treatment and every 12 weeks thereafter for 12 months ]
      Complete response + partial response


    Current Secondary Outcome:

    • Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) [ Time Frame: Baseline up to EOT (Up to 15 months) ]
      Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA and nATA development) using a laboratory test. ATA-positive samples were further characterized as transiently ATA positive (defined as 1 or 2 post-Baseline ATA-positive responses), persistently ATA positive (defined as more than 2 post-Baseline ATA positive responses), and nATA positive or negative.
    • Overall Response Rate (ORR) (Phase 1) [ Time Frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months) ]
      Overall response rate is defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
    • Time to Progression (TTP) (Phase 1 and 2) [ 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) ]
      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 to Response (Phase 1 and 2) [ Time Frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months) ]
      Time to response is defined as the time in months from the first dose of study treatment until the date of the first assessment of confirmed CR or PR. as assessed by an IRF using IWG revised response criteria for malignant lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
    • Duration of Response (DOR) (Phase 1 and 2) [ 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) ]
      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.
    • Event Free Survival (EFS) (Phase 1 and 2) [ 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) ]
      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.
    • Progression Free Survival (PFS) (Phase 1 and 2) [ 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) ]
      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. and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
    • Overall Survival (OS) (Phase 1 and 2) [ Time Frame: Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrollment of the last participant (Up to 60 months) ]
      OS is the time in months from start of study treatment to date of death due to any cause.
    • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) [ Time Frame: From the first dose through 30 days after the last dose of study medication (up to 15 months) ]
      An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Cri

      Original Secondary Outcome:

      • Anti-therapeutic antibody (ATA) titer and neutralizing ATA titer (phase 1 & phase 2) [ Time Frame: At screening, predose Day 1 at Cycle 2 and Cycle 4, and at end of treatment; approximately 28 months ]
        Immunogenicity of brentuximab vedotin
      • Number of patients with overall response as determined by an IRF using PET, CT and, clinical assessment according to IWG revised response criteria (phase 1) [ Time Frame: PET: At Screening, Cycles 2 and 7. No additional scans needed after Cycle 7 unless clinically indicated. CT: Screening, Cycle 2, 4, 7, 10, 13, 16 and end of treatment and every 12 weeks therafter for 12 months ]
        Complete response + partial response
      • Time to progression (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to the date of first documented progressive disease, approximately 40 months ]
      • Time to response (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to the date of first documentation of a confirmed complete or partial response, approximately 12 months ]
      • Duration of response (phase 1 & phase 2) [ Time Frame: From the date of first documentation of a confirmed response to the date of progressive disease, approximately 12 months ]
      • Number of patients with event-free survival (phase 1 & phase 2) [ Time Frame: Duration of study (up to 16 cycles) and for 12 months following last dose; approximately 40 months ]
      • Number of patients with progression-free survival (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to the date of first documented progressive disease or death, approximately 40 months ]
      • Number of patients with overall survival (phase 2) [ Time Frame: From the first dose of study treatment to date of death, approximately 40 months ]
      • Adverse events, serious adverse events, assessments of clinical and laboratory values, and vital sign measurements (phase 2) [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 12 months ]
      • Plasma concentrations of brentuximab vedotin, total therapeutic antibody, and monomethyl auristatin E (MMAE) (phase 2) [ Time Frame: All Cycles: Day 1; Cycle 1: Days 2, 3, 5, 14; Cycle 2: Days 2 (phase 1 only), 3, 5; Cycle 8: Days 2, 3, 5, 14 ]
        Pharmacokinetics of brentuximab vedotin


      Information By: Takeda

      Dates:
      Date Received: December 12, 2011
      Date Started: April 16, 2012
      Date Completion: March 20, 2018
      Last Updated: April 5, 2017
      Last Verified: April 2017