Tisagenlecleucel Versus Standard of Care in Adult Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma: A Randomized, Open Label, Phase III Trial (BELINDA)
Tisagenlecleucel Versus Standard of Care in Adult Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma: A Randomized, Open Label, Phase III Trial (BELINDA)
This is a randomized, open label, multicenter phase III trial comparing the efficacy, safety, and tolerability of tisagenlecleucel to Standard Of Care in adult patients with aggressive B-cell Non-Hodgkin Lymphoma after failure of rituximab and anthracycline containing frontline immunochemotherapy.
Approximately 318 subjects were planned to be randomized; 322 subjects were analyzed (Full analysis set): 162 subjects in the tisagenlecleucel arm and 160 subjects in the SOC arm.
The target population consisted of adult participants with aggressive B-cell non-Hodgkin lymphoma (NHL) who were relapsed/refractory within 365 days of their last dose of first line immunochemotherapy and eligible for autologous hematopoietic stem cell transplantation (HSCT).
The duration of treatment in the tisagenlecleucel treatment strategy is from the start of bridging chemotherapy (if applicable) until the infusion of tisagenlecleucel (expected on average at approximately 6 weeks from randomization). The duration of the treatment in the SOC treatment strategy is from the start of salvage chemotherapy until autologous HSCT. In either treatment arm, if infusion of tisagenlecleucel or autologous HSCT is not possible, the duration of treatment is until the last dose of study treatment prior to discontinuation of the treatment strategy.
Inclusion Criteria:
Histologically confirmed, aggressive B-cell NHL at relapse/progression or PR after front line therapy. Aggressive B-cell NHL is heretofore defined by the following list of subtypes (Swerdlow et al 2016):
Relapse or progression within 365 days from last dose of anti CD20 antibody and anthracycline containing first line immunochemotherapy or refractory (have not achieved a CR).
Patient is considered eligible for autologous HSCT as per local investigator assessment. Note: Intention to transplant and type of high dose chemotherapy (HDCT) regimen will be documented at the time of study entry
Disease that is both active on PET scan (defined as 5-Deauville scorepoint-scale of 4 or 5) and measurable on CT scan, defined as::
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate organ function:
Renal function defined as:
Hepatic function defined as:
Hematologic Function (regardless of transfusions) defined as:
Adequate pulmonary function defined as:
Exclusion Criteria:
Prior treatment with anti-CD19 therapy, T cell therapy, or any prior gene therapy product
Treatment with any systemic lymphoma-directed second line anticancer therapy prior to randomization. Only steroids and local irradiation are permitted for disease control
Patients with active central nervous system (CNS) involvement by disease under study are excluded, except if the CNS involvement has been effectively treated and local treatment was >4 weeks before randomization
Prior allogeneic HSCT
Clinically significant active infection
Any of the following cardiovascular conditions:
Patients with active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré Syndrome (GBS), Amyotrophic Lateral Sclerosis (ALS)) and clinically significant active cerebrovascular disorders (e.g. cerebral edema, posterior reversible encephalopathy syndrome (PRES))