This phase II trial compares the impact of brentuximab vedotin and nivolumab after radiation to standard of care high dose chemotherapy (HDT)-autologous stem cell transplant (ASCT) in standard-risk patients with classic Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). In addition, the phase III trial will compare the effect of pembrolizumab after HDT-ASCT to standard of care HDT-ASCT alone in high-risk patients with relapsed or refractory classic Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. An ASCT is a procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person. Giving HDT before an ASCT helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Radiation therapy (RT) uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving brentuximab vedotin and nivolumab after radiation may be safe, tolerable and more effective than standard of care HDT-ASCT in treating patients with standard risk relapsed or refractory classic Hodgkin lymphoma. In addition, giving pembrolizumab after standard of care HDT-ASCT may be safe and tolerable and more effective than HDT-ASCT alone in treating high-risk patients with relapsed or refractory classic Hodgkin lymphoma.
STEP 0 REGISTRATION: Patient must have biopsy confirmed relapsed classical Hodgkin lymphoma
STEP 0 REGISTRATION: Patient must be 5-75 years of age
STEP 0 REGISTRATION: Patient must have relapsed/refractory classical Hodgkin lymphoma (R/R cHL) after first line of chemotherapy
STEP 0 REGISTRATION: Patients > 17 years of age must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and patients ≤ 17 years of age must have a Lansky performance status 50-100
None
Parallel
3-Dimensional Conformal Radiation Therapy
RadiationUndergo 3DCRT
Autologous Hematopoietic Stem Cell Transplantation
Procedure/SurgeryUndergo ASCT
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Brentuximab Vedotin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT and PET/CT
High Dose Chemotherapy
DrugReceive HDT
Intensity-Modulated Radiation Therapy
RadiationUndergo IMRT
Nivolumab
Biological/VaccineGiven IV
Pembrolizumab
Biological/VaccineGiven IV
Pencil Beam Scanning
RadiationUndergo pencil beam proton RT
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Salvage Therapy
Procedure/SurgeryReceive standard of care salvage therapy
Scattering Proton Beam Therapy
RadiationUndergo passive scattering proton RT
Tomotherapy
RadiationUndergo tomotherapy
Uniform Active Scanning Proton Beam Therapy
RadiationUndergo uniform scanning proton RT
Volume Modulated Arc Therapy
RadiationUndergo VMAT
Progression-free survival (PFS) (Standard risk cohort)
The analysis will be performed using the repeated confidence intervals methodology. Two-sided repeated confidence interval will be constructed using the partial likelihood estimate from stratified Cox proportional hazards model and the critical value based on the Lan-DeMets error-spending function that corresponds to the truncated O'Brien-Fleming boundaries. Sensitivity analysis will be performed to assess the possible impact of treatment non-compliance. The actual treatment received may be considered in a multivariable Cox model where possible effects of clinical and biological characteristics on outcome are assessed.
PFS (High-risk cohort)
Stratified log-rank test will be used for the primary analysis to compare the PFS between arms D and C.
Overall survival (OS) (Standard risk cohort)
The analysis will be performed using the stratified log-rank test. To preserve the overall type I error rate, critical values at the interim efficacy analyses will be determined using a truncated version of the Lan-DeMets error spending function corresponding to the O'Brien-Fleming boundary.
OS (High risk cohort)
Stratified log-rank test will be used to compare the OS between the two arms.
Incidence of adverse events
Will be measured using the most recent version of the Common Terminology Criteria for Adverse Events.
Estimates of treatment effects by sex
Estimates of the primary outcome treatment effect and the corresponding 95% confidence intervals (CIs) by sex.
Estimates of treatment effects by race
Estimates of the primary outcome treatment effect and the corresponding 95% CIs by race.
Estimates of treatment effects by ethnicity
Estimates of the primary outcome treatment effect and the corresponding 95% CIs by ethnicity.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
