It is an open-label, multicenter, phase II, single arm trial to Evaluate Activity and Safety of Daratumumab in combination with Bortezomib and Dexamethasone in patients about 28 patients with Relapsed or Refractory Plasmablastic lymphoma.
Histologically confirmed plasmablastic lymphoma according to WHO 2017, CD38-positive by immunohistochemistry (≥5% of positive cells) Local diagnosis of PBL and local CD38 assessment ≥5% will suffice for enrollment and start of treatment.
after at least one line of conventional-dose chemotherapy followed or not by autologous stem cell transplantation;
after at least one line of conventional-dose chemotherapy and not eligible for salvage autologous or allogeneic transplantation;
ECOG Performance Status ≤ 3;
Histologic diagnosis different from confirmed plasmablastic lymphoma according to WHO 2017 and/or CD38 expression < 5% of positive cells
CNS involvement
Patients with known hypersensitivity to the investigational drug or to product components or severe allergic or anaphylactic reactions to humanized products
Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy including targeted small molecule agents within 14 days prior to the first dose of study drug
Single group
Daratumumab
DrugInduction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen). Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.
Bortezomib
DrugInduction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen). Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.
Dexamethasone
DrugInduction phase planning one course (cycle 1) of daratumumab as single agent followed by 8 courses (cycles 2-9) of daratumumab in combination with bortezomib and dexamethasone (DVd regimen). Patients achieving at least a SD after induction will be addressed to the maintenance phase, planning a maximum of 6 cycles (cycles 10-15) of daratumumab as single agent.
Overall response rate (ORR)
Response assessment will be done at each restaging. The best overall response will be defined as the best response between the date of beginning of therapy and the last response evaluation. Patients without response assessment (due to whatever reason) will be considered as non-responders.
Progression-free survival (PFS)
From the date of starting therapy and the date of disease progression, relapse or death from any cause. Responding patients according to the Lugano classification response Criteria and patients who are lost to follow-up will be censored at their last assessment date.
Overall survival (OS)
From the date of starting therapy and the date of death from any cause. Patients alive and those who are lost to follow-up at the time of the final analysis will be censored at the date of the last contact.
Duration of response (DOR)
For all patients who achieved a response (CR or PR) according to Response Criteria for NHL with PET (Lugano 2014) and it is measured from the date when criteria for response are met (CR or PR) until the date of progression (including death due to progression) or relapse. Patients without relapse or progression or with death from other cause than progression will be censored at their last assessment date.
Number of participants with treatment-related adverse events as assessed by current version of CTCAE.
The safety of daratumumab as single agent and in combination with bortezomib/dexamethasone will be assessed in all patients who have received at least one dose of study medication. Rates of adverse events and of serious adverse events will be will be presented with two sided 95% confidence intervals.
Click on the lead sponsor to view all of their trials.
Fondazione Italiana Linfomi - ETS
Lead sponsor
Janssen-Cilag S.p.A.
Collaborator
