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.
This is an open-label, multicenter, phase II, single arm trial. Patients will be recruited over 18 months in 19 FIL centers and it is expected that a total of 28 patients will start treatment. Analysis of the primary endpoint of the study is planned approximately after 12 months from the enrollment of the last patient, regardless of the response to protocol treatment of this patient. The total duration of the study is 60 months (\~5 years). Patients will be enrolled based on the local diagnosis and the local assessment of CD38 expression ≥ 5%. The screening phase of the study includes baseline assessments according to local practice and those required by the study. Samples coming from the most recent biopsy, and if available also those used for the first diagnosis, are to be collected and sent afterwards, upon request of the FIL Offices, to one of the three FIL designed central laboratories. Central diagnosis review and CD38 assessment will be performed during or at the end of the study conductance; there's no need to wait for central results to start protocol treatment. Protocol treatment consists of an induction phase planning one course (cycle 1) of daratumumab sc as single agent followed by 8 courses (cycles 2-9) of daratumumab sc in combination with bortezomib sc 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 sc as single agent. Induction cycles will be administered every 21 days, while maintenance cycles will be administered every 28 days. Treatment with DVd or daratumumab single agent will be discontinued before completion of planned cycles in case of disease progression, unacceptable toxicity, withdrawal of consent and/or the investigator determines that further therapy is not in the patient best interest (e.g., due to non-compliance, toxicity, etc.). Adverse events according to CTCAE will be monitored from the first dose of induction treatment, throughout maintenance phase and for 30 days after the last dose of protocol treatment with the study drug or 30 days after the last dose of drug in case of early discontinuation from any cause.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Induction 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.
Induction 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.
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
Ancona, Ancona, Italy
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.
Time frame: 30 months
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.
Time frame: 30 months
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.
Time frame: 30 months
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.
Time frame: 30 months
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.
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Induction 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.
Aviano - IRCCS Centro di Riferimento Oncologico di Aviano - Divisione di Oncologia e dei Tumori immuto-correlati
Aviano, Aviano, Italy
RECRUITINGAzienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia
Florence, Firenze, Italy
RECRUITINGMilano - ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia
Miano, Italy, Italy
RECRUITINGMonza - ASST MONZA Ospedale S. Gerardo - Ematologia
Monza, Italy, Italy
RECRUITINGNapoli - AORN - Azienda Ospedaliera dei Colli Monald - U.O.C. Oncologia
Naples, Italy, Italy
ACTIVE_NOT_RECRUITINGRoma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive
Roma, Italy, Italy
NOT_YET_RECRUITINGRoma - Ospedale S. Camillo - Ematologia
Roma, Italy, Italy
RECRUITINGA.O. Universitaria Policlinico Giaccone Di Palermo
Palermo, Palermo, Italy
NOT_YET_RECRUITINGA.O. Universitaria Citta' Della Salute E Della Scienza Di Torino
Torino, Torino, Italy
RECRUITING...and 8 more locations
Time frame: 30 months
Rate of Complete Remission (CRR)
Comparison of ORR and CRR before and after maintenance, and by evaluation of rate of conversion of SD to PR and of SD/PR to CR with daratumumab maintenance.
Time frame: 30 months
Relationship between CD38 expression on lymphoma cells, assessed by immunohistochemistry, and the response rate.
The extent of CD38 expression evaluated by immunochemistry on the diagnostic biopsy-tissue will be correlated with response measured according to the Lugano 2014 criteria at various timepoints: after induction cycle 1, after induction cycles 3, 6 and 9 (end of induction, EOI); after maintenance cycles 12 and 15 (end of treatment, EOT). correlated with response measured according to the Lugano 2014 criteria at various endpoints.
Time frame: 30 months
Impact of daratumumab and bortezomib treatment on biological cell profiles.
The impact of daratumumab and bortezomib treatment in immune activation (CD38, CD25, HLA-DR), T cell differentiation (naïve, central memory, effector memory and terminal effector memory T cell subset) and on circulating myeloid-derived suppressor cells (MDSC) as well as Treg will be evaluated by multiparametric flow cytometry (84 multiple staining). Peripheral blood samples will be collected in different timepoints: before treatment start; after cycle 1; after cycle 3 and at EOT.
Time frame: 30 months