Hodgkin lymphoma (HL), a neoplasm of lymphoid tissue which is histopathologically defined by the presence of malignant Hodgkin Reed-Sternberg (HRS) cells in a background of inflammatory cells. The proposed pediatric study has been designed to evaluate brentuximab vedotin as a component of a multiagent frontline chemotherapy regimen in patients with advanced stage, newly diagnosed HL, here defined as Stage III and Stage IV and a =50 Lansky Play-Performance or Karnofsky Performance Status. MedDRA
Conditions
Sponsors
Millennium Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Criteria for Inclusion: Male or female patients aged 5 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 Primary Objective: ? To assess the safety and tolerability, and to identify the recommended dose of brentuximab vedotin when combined with multiagent chemotherapy regimen AVD for first-line treatment of advanced stage HL in pediatric patients. Phase 2 Primary Objectives: ? To evaluate the CR rate of pediatric patients with advanced stage HL at the end of protocol therapy. ? To determine the percentage of patients who are PET- after 2 cycles of protocol therapy. ? To evaluate the PR rate of pediatric patients with advanced stage HL at the end of protocol therapy. ? To evaluate the ORR of pediatric patients with advanced stage HL at the end of protocol therapy. ? To determine the percentage of patients who are able to complete 6 cycles of protocol therapy at the recommended dose.;Secondary Objective: Phase 1 Secondary Objectives: ? To describe the maximum observed concentration (Cmax), area under the concentration-time curve from time 0 to 15 days (AUC0-15), and time of first time of occurrence of Cmax (Tmax) of brentuximab vedotin, monomethyl auristatin E (MMAE), and total (free and conjugated) therapeutic antibody (TAb). For further - please refer to Protocol Phase 2 Secondary Objectives: ? To evaluate the progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and duration of response (DOR) in pediatric patients with advanced stage HL treated with protocol therapy. For further - please refer to Protocol;Primary end point(s): Phase 1 Primary Endpoints ? Determination of the recommended dose of brentuximab vedotin in combination with AVD in a pediatric population. ? 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. ? 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. Phase 2 Primary Endpo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1 Secondary Endpoints ? Mean Cmax and mean AUC0-15 of brentuximab vedotin (serum), TAb (serum), and MMAE (plasma). ? Median Tmax of brentuximab vedotin (serum), TAb (serum), and MMAE (plasma). ? Percentage of patients who achieve a CR per independent review facility (IRF) assessment at End of Treatment (EOT) per International Working Group (IWG) criteria. ? Percentage of patients who achieve a PR per IRF assessment at EOT per IWG criteria. ? Percentage of patients who achieve an overall response (OR) per IRF assessment at EOT per IWG criteria. ? Percentage of patients whose disease is PET- after 2 cycles of protocol therapy per IRF assessment. ? Percentage of patients whose disease is PET+ after 6 cycles of protocol therapy per IRF assessment. ? 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. ? Impact of ATA and nATA on the safety, efficacy, and PK endpoints. Phase 2 Secondary Endpoints ? PFS, EFS, OS, DOR. ? Percentage of patients receiving irradiation for HL following study treatment. ? 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. ? 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. ? 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. ? Impact of ATA and nATA on the safety, efficacy, and PK endpoints. ? Mean Cmax and mean AUC0-15 of brentuximab vedotin (serum), TAb (serum), and MMAE (pla | — |
Countries
Bulgaria, Canada, Italy, Spain, United States
Contacts
Public ContactResponsible Medical Officer
Millennium Pharmaceuticals Inc.
Outcome results
None listed