Clinical Trials /

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

NCT02979522

Description:

The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as 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).

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Participants With Advanced Stage Newly Diagnosed Hodgkin Lymphoma
  • Official Title: An Open-Label Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Patients With Advanced Stage Newly Diagnosed Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: C25004
  • SECONDARY ID: 2015-004112-38
  • SECONDARY ID: U1111-1171-0984
  • NCT ID: NCT02979522

Conditions

  • Hodgkin Disease

Interventions

DrugSynonymsArms
Brentuximab vedotinAdcetrisBrentuximab vedotin 48 mg/m^2
DoxorubicinAdriamycinBrentuximab vedotin 48 mg/m^2
VinblastineBrentuximab vedotin 48 mg/m^2
DacarbazineBrentuximab vedotin 48 mg/m^2

Purpose

The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as 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).

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 approximately 55 evaluable participants. The study will be conducted in
      2 phases, Phase 1 and Phase 2. Phase 1 study will enroll up to 12 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
      approximately 55, including participants treated at recommended dose in Phase 1. Participants
      will be enrolled in the following 2 dose Cohorts:

      • Brentuximab vedotin 48 mg/m^2 or 36 mg/m^2 in combination with doxorubicin, vinblastine,
      and dacarbazine.

      Phase 1 has completed enrollment and Phase 2 is now open for enrollment.

      This multi-center trial will be conducted in United States (US), Italy, Brazil, Japan,
      Taiwan, Singapore, and Hong Kong. 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 until death or study closure or a maximum of 2 years after
      enrollment of the last participant.
    

Trial Arms

NameTypeDescriptionInterventions
Brentuximab vedotin 48 mg/m^2ExperimentalBrentuximab 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.
  • Brentuximab vedotin
  • Doxorubicin
  • Vinblastine
  • Dacarbazine

Eligibility Criteria

        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.

        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.
      
Maximum Eligible Age:17 Years
Minimum Eligible Age:5 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Determination of the Recommended Dose of Brentuximab Vedotin in Combination With doxorubicin, vinblastine, and dacarbazine in a Pediatric Population
Time Frame:Up to 6 months
Safety Issue:
Description:The recommended dose of brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine for a pediatric population on the basis of the safety, tolerability, and preliminary pharmacokinetic (PK) and efficacy data (if available).

Secondary Outcome Measures

Measure:Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Brentuximab Vedotin (Serum), Total (free and conjugated) Therapeutic Antibody (TAb) (Serum), and Monomethyl Auristatin E (MMAE) (Plasma)
Time Frame:Up to 15 days
Safety Issue:
Description:Mean maximum concentration from Day 0 to Day 15 for brentuximab vedotin and TAb in serum and MMAE in plasma based on data from the PK population.
Measure:Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15)
Time Frame:Up to 15 days
Safety Issue:
Description:Mean AUC from Day 0 to Day 15 for brentuximab vedotin and TAb in serum and MMAE in plasma based on data from the PK population.
Measure:Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin (serum), TAb (serum), and MMAE (plasma)
Time Frame:Up to 15 days
Safety Issue:
Description:First time of occurrence of maximum (peak) concentration for a single dose of brentuximab vedotin for participants in the PK population.
Measure:Phase 1: Percentage of Participants who Achieve a CR per IRF Assessment at EOT per IWG Criteria
Time Frame:Up to 7 months
Safety Issue:
Description:Percentage of participants in the response-evaluable population who achieve a complete response based on the IRF assessment at the EOT visit based on the IWG criteria.
Measure:Phase 1: Percentage of Participants who Achieve a PR per IRF Assessment at EOT per IWG Criteria
Time Frame:Up to 7 months
Safety Issue:
Description:Percentage of participants in the response-evaluable population who achieve a partial response based on the IRF assessment at the EOT visit based on the IWG criteria.
Measure:Phase 1: Percentage of Participants who Achieve an OR per IRF Assessment at EOT per IWG Criteria
Time Frame:Up to 7 months
Safety Issue:
Description:Percentage of participants in the response-evaluable population who achieve an overall response based on the IRF assessment at the EOT visit based on the IWG criteria.
Measure:Phase 1: Percentage of Participants Whose Disease is PET Negative after 2 Cycles of Protocol Therapy per IRF Assessment
Time Frame:Up to 2 months
Safety Issue:
Description:Percentage of participants in the response evaluable population whose disease is negative per PET after 2 cycles of protocol therapy per IRF assessment.
Measure:Phase 1: Percentage of Participants Whose Disease is PET Positive After 6 Cycles of Protocol Therapy per IRF Assessment
Time Frame:Up to 6 months
Safety Issue:
Description:Percentage of participants in the response-evaluable population whose disease is positive per PET after 6 cycles of protocol therapy per IRF assessment.
Measure:Phase 1: Percentage of Participants who are Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive
Time Frame:Up to 7 months
Safety Issue:
Description:Percentage of participants in the safety population who are ATA positive, persistently positive, or transiently positive, and nATA positive.
Measure:Phase 2: Progression-free Survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 2: Event-free Survival (EFS)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 2: Overall Survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 2: Duration of Response (DOR)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment
Time Frame:Up to 24 months
Safety Issue:
Description:Percentage of participants receiving irradiation for HL after up to 6 months of study treatment.
Measure:Phase 2: Percentage of Participants who Experience AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
Time Frame:Up to 7 months
Safety Issue:
Description:The percentage of participants in the safety population who experience TEAEs for up to 6 months of treatment plus 30 days following the end of study treatment.
Measure:Phase 2: Percentage of Participants who Experience SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
Time Frame:Up to 7 months
Safety Issue:
Description:The percentage of participants in the safety population who experience treatment-emergent SAEs for up to 6 months of treatment plus 30 days following the end of study treatment.
Measure:Phase 2: Percentage of Participants who are ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive
Time Frame:Up to 7 months
Safety Issue:
Description:Percentage of participants in the safety population who are ATA positive, persistently positive, or transiently positive, and nATA positive.
Measure:Phase 2: Mean Cmax of Brentuximab Vedotin (Serum), TAb (Serum), and MMAE (Plasma)
Time Frame:Up to 15 days
Safety Issue:
Description:Mean maximum concentration from Day 0 to Day 15 for brentuximab vedotin and TAb in serum and MMAE in plasma based on data from the PK population.
Measure:Phase 2: Mean AUC0-15 of Brentuximab Vedotin (Serum), TAb (Serum), and MMAE (Plasma)
Time Frame:Up to 15 days
Safety Issue:
Description:Mean AUC from Day 0 to Day 15 for brentuximab vedotin and TAb in serum and MMAE in plasma based on data from the PK population.
Measure:Phase 2: Median Tmax of Brentuximab Vedotin (Serum), TAb (Serum), and MMAE (Plasma)
Time Frame:Up to 15 days
Safety Issue:
Description:First time of occurrence of maximum (peak) concentration for a single dose of brentuximab vedotin for participants in the PK population.
Measure:Phase 2: Percentage of Participants who Experience Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy Through Study Closure
Time Frame:Up to 24 months
Safety Issue:
Description:Percentage of participants who experience peripheral neuropathy, regardless of seriousness, from the first dose of protocol therapy through study closure.
Measure:Phase 2: Time to Onset and Time to Resolution for all Peripheral Neuropathy Events
Time Frame:Up to 24 months
Safety Issue:
Description:Time from first dose of protocol therapy to onset, and time from onset to resolution for all peripheral neuropathy events.
Measure:Phase 2: Immune Reconstitution Over Time
Time Frame:Up to 24 months
Safety Issue:
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).
Measure:Phase 1: ATA Titer
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:Phase 2: ATA Titer
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1: Percentage of Participants Achieving CR per IRF Assessment per IWG Criteria in ATA Positive and ATA Negative Participants
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1: Incidence and Severity of AEs and SAEs in ATA Positive and ATA Negative Participants
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 2: Percentage of Participants Achieving CR per IRF Assessment per IWG Criteria in ATA Positive and ATA Negative Participants
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 2: Incidence and Severity of AEs and SAEs in ATA Positive and ATA Negative participants
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug therapy, pediatric Hodgkin disease, frontline Hodgkin disease, advanced stage Hodgkin disease, pediatric lymphoma

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