brentuximab vedotin for Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Main Criteria for Inclusion: Male or female patients aged 5 to <18 years with newly diagnosed classical CD30+ advanced stage (Stage III and Stage IV) HL who are treatment naïve with Karnofsky Performance Status or Lansky Play- Performance ≥50."}

Exclusion criteria

• {"criterion_text":"- Main Criteria for Exclusion: Patients may not have nodular lymphocyte-predominant HL, known active cerebral meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML, sensory or motor peripheral neuropathy, or known hypersensitivity to brentuximab vedotin or any component of AVD."}

Primary endpoints

• {"endpoint_text":"- Phase 1: Determination of the recommended dose of brentuximab vedotin in combination with AVD in a pediatric population.","definition_or_measurement_approach":"Dose-determination based on safety and tolerability assessments in Phase 1 (to identify recommended dose for combination with AVD)."}
• {"endpoint_text":"- Phase 1: Percentage of patients who experience AEs from the first dose of protocol therapy through 30 days after administration of the last dose of protocol therapy.","definition_or_measurement_approach":"Adverse events recorded from first dose through 30 days after last dose; percentage calculation of patients experiencing AEs in that window."}
• {"endpoint_text":"- Phase 1: Percentage of patients who experience serious AEs (SAEs) from the first dose of protocol therapy through 30 days after administration of the last dose of protocol therapy.","definition_or_measurement_approach":"Serious adverse events recorded from first dose through 30 days after last dose; percentage calculation of patients experiencing SAEs in that window."}
• {"endpoint_text":"- Phase 2: Percentage of patients who achieve a CR per IRF assessment at EOT per IWG criteria.","definition_or_measurement_approach":"Complete response assessed by an Independent Review Facility (IRF) at End Of Treatment (EOT) using International Working Group (IWG) criteria."}
• {"endpoint_text":"- Phase 2: Percentage of patients whose disease is PET- after 2 cycles of protocol therapy per IRF assessment.","definition_or_measurement_approach":"PET negativity assessed by IRF after 2 cycles of protocol therapy; percentage of patients PET-."}
• {"endpoint_text":"- Phase 2: Percentage of patients who achieve a PR per IRF assessment at EOT per IWG criteria.","definition_or_measurement_approach":"Partial response assessed by IRF at EOT per IWG criteria; percentage calculation."}
• {"endpoint_text":"- Phase 2: Percentage of patients who achieve an OR per IRF assessment at EOT per IWG criteria.","definition_or_measurement_approach":"Overall response (OR) assessed by IRF at EOT per IWG criteria; percentage calculation."}
• {"endpoint_text":"- Phase 2: Percentage of patients who are able to complete 6 cycles of protocol therapy at the recommended dose.","definition_or_measurement_approach":"Proportion of patients completing 6 cycles of protocol therapy at the recommended dose determined in Phase 1."}

Secondary endpoints

• {"endpoint_text":"- Phase 1: Mean Cmax and mean AUC0-15 of brentuximab vedotin (serum), TAb (serum), and MMAE (plasma).","definition_or_measurement_approach":"Pharmacokinetic measures: mean maximum concentration (Cmax) and area under curve (AUC0-15) for analytes in serum/plasma."}
• {"endpoint_text":"- Phase 1: Median Tmax of brentuximab vedotin (serum), TAb (serum), and MMAE (plasma).","definition_or_measurement_approach":"Pharmacokinetic measure: median time to reach Cmax (Tmax) for listed analytes."}
• {"endpoint_text":"- Phase 1: Percentage of patients who achieve a CR per independent review facility (IRF) assessment at End of Treatment (EOT) per International Working Group (IWG) criteria.","definition_or_measurement_approach":"CR assessed by IRF at EOT per IWG criteria; percentage calculation."}
• {"endpoint_text":"- Phase 1: Percentage of patients who achieve a PR per IRF assessment at EOT per IWG criteria.","definition_or_measurement_approach":"PR assessed by IRF at EOT per IWG criteria; percentage calculation."}
• {"endpoint_text":"- Phase 1: Percentage of patients who achieve an overall response (OR) per IRF assessment at EOT per IWG criteria.","definition_or_measurement_approach":"OR assessed by IRF at EOT per IWG criteria; percentage calculation."}
• {"endpoint_text":"- Phase 1: Percentage of patients whose disease is PET- after 2 cycles of protocol therapy per IRF assessment.","definition_or_measurement_approach":"PET negativity after 2 cycles assessed by IRF; percentage calculation."}
• {"endpoint_text":"- Phase 1: Percentage of patients whose disease is PET+ after 6 cycles of protocol therapy per IRF assessment.","definition_or_measurement_approach":"PET positivity after 6 cycles assessed by IRF; percentage calculation."}
• {"endpoint_text":"- Phase 1: Percentage of patients who are ATA positive, persistently positive, or transiently positive, ATA titer and neutralizing ATA (nATA) positive at baseline, predose Cycle 2 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, or at termination if treatment is terminated before Cycle 6, and at EOT","definition_or_measurement_approach":"Immunogenicity assessments for anti-therapeutic antibodies (ATA) and neutralizing ATA at specified timepoints; categorical reporting of positivity and titers."}
• {"endpoint_text":"- Phase 1: Impact of ATA and nATA on the safety, efficacy, and PK endpoints.","definition_or_measurement_approach":"Analysis of correlation/impact of ATA/nATA status on safety, efficacy, and pharmacokinetic endpoints."}
• {"endpoint_text":"- Phase 2: PFS, EFS, OS, DOR.","definition_or_measurement_approach":"Time-to-event endpoints: progression-free survival, event-free survival, overall survival, duration of response as per protocol-defined criteria."}
• {"endpoint_text":"- Phase 2: Percentage of patients receiving irradiation for HL following study treatment.","definition_or_measurement_approach":"Proportion of patients who receive radiotherapy for Hodgkin lymphoma after completion of study treatment."}
• {"endpoint_text":"- Phase 2: Percentage of patients who experience AEs from the first dose of protocol therapy through 30 days after administration of the last dose of protocol therapy.","definition_or_measurement_approach":"Adverse events recorded from first dose through 30 days after last dose; percentage calculation."}
• {"endpoint_text":"- Phase 2: Percentage of patients who experience SAEs from the first dose of protocol therapy through 30 days after administration of the last dose of protocol therapy.","definition_or_measurement_approach":"Serious adverse events recorded from first dose through 30 days after last dose; percentage calculation."}
• {"endpoint_text":"- Phase 2: Percentage of patients who are ATA positive, persistently positive, or transiently positive, ATA titer and nATA positive at baseline, predose Cycle 2 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, or at termination if treatment is terminated before Cycle 6, and at EOT.","definition_or_measurement_approach":"Immunogenicity assessments for ATA and nATA at specified timepoints; categorical reporting."}
• {"endpoint_text":"- Phase 2: Impact of ATA and nATA on the safety, efficacy, and PK endpoints.","definition_or_measurement_approach":"Analysis of the impact of ATA/nATA on safety, efficacy, and pharmacokinetic outcomes."}
• {"endpoint_text":"- Phase 2: Mean Cmax and mean AUC0-15 of brentuximab vedotin (serum), TAb (serum), and MMAE (plasma).","definition_or_measurement_approach":"Pharmacokinetic measures: mean Cmax and mean AUC0-15 for listed analytes."}
• {"endpoint_text":"- Phase 2: Median Tmax of brentuximab vedotin (serum), TAb (serum), and MMAE (plasma).","definition_or_measurement_approach":"Pharmacokinetic measure: median Tmax for listed analytes."}
• {"endpoint_text":"- Phase 2: Percentage of patients who experience peripheral neuropathy, regardless of seriousness, from the first dose of protocol therapy through study closure.","definition_or_measurement_approach":"Incidence and timing of peripheral neuropathy events from first dose through study closure; percentage calculation."}
• {"endpoint_text":"- Phase 2: Time to onset and time to resolution for all peripheral neuropathy events.","definition_or_measurement_approach":"Time-to-event measures for onset and resolution of peripheral neuropathy."}
• {"endpoint_text":"- Phase 2: Immune reconstitution (peripheral blood CD34+ count; enumeration of the total lymphocyte count and lymphocyte subsets; total Ig and IgG, IgM, and IgA levels; and levels of the antibodies to tetanus, HiB, and polio serotypes) at baseline, EOT, and at 6, 12, and 18 months (±1 month) after last dose, until the start of subsequent anticancer therapy (with the exception of radiotherapy administered as part of first-line therapy).","definition_or_measurement_approach":"Laboratory-based immune reconstitution assessments at specified timepoints (baseline, EOT, and follow-up months) measuring cellular and humoral immunity parameters."}

Italy

Earliest CTIS Part Ii Submission Date

26-10-2023

Latest Decision Or Authorization Date

01-04-2025

Processing Time Days

523

Number Of Sites

4

Number Of Participants

15

Primary sponsor

Full Name

Takeda Development Center Americas Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Codes: 1,10,12,2,6

Name

Ppd Inc.

Responsibilities

Code: 8

Name

Almac Clinical Services Limited

Responsibilities

Code: 14

Name

Medidata Solutions Inc.

Responsibilities

Code: 7

Name

Cognizant Technology Solutions India Private Limited

Responsibilities

Code: 8

Name

Azenta US Inc.

Responsibilities

Sample storage

Third parties

• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Codes: 1,10,12,2,6","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Cognizant Technology Solutions India Private Limited","duties_or_roles":"Code: 8","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"Code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Code: 7","organisation_type":"Non-Pharmaceutical company"}