This is a multi-center, phase II study to evaluate the efficacy and safety of CTL019 in Chinese adult patients with relapsed or refractory DLBCL.
Disease assessments will be performed at screening, after bridging, 1, 3, 6, 9 and 12 months after tisagenlecleucel infusion, and every 6 months in the second year, and annually up to 60 months after infusion. Efficacy will be assessed until progression; safety will be assessed throughout the study. A long term follow-up up to 15 years after CTL019 infusion will continue under a separate protocol (CCTL019A2205B)(NCT02445222).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
A single intravenous (i.v.) infusion of 0.6 - 6.0×10\^8 CAR positive viable T cells.
Overall Response Rate (ORR)
Complete Response (CR) and Partial Response (PR) according to the Lugano classification as determined by the Investigator.
Time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Duration of Response (DOR)
Time from CR or PR, whichever occurs first, to relapse or death due to DLBCL.
Time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Time to response (TTR)
Time from tisagenlecleucel infusion to CR or PR, whichever occurs first.
Time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Progression-Free Survival (PFS)
Time from tisagenlecleucel infusion to the first documented disease progression or death due to any cause.
Time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Event free survival (EFS)
Time from tisagenlecleucel infusion to the first documented disease progression or relapse, new treatment for lymphoma or death due to any cause.
Time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Overall Survival (OS)
Time from tisagenlecleucel infusion to death due to any cause.
Time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
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Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths
Analysis of absolute and relative frequencies for treatment emergent AE, SAE and Deaths by primary System Organ Class (SOC) through the monitoring of relevant clinical and laboratory safety parameters.
Time frame: From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months
Tisagenlecleucel immunogenicity (humoral)
The humoral immunogenicity assay will be evaluated to measure the antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.
Time frame: Up to Month 60
Tisagenlecleucel immunogenicity (cellular)
The cellular immunogenicity assay will be evaluated to assess the presence of T lymphocytes activated by the tisagenlecleucel protein.
Time frame: Up to Month 60
In vivo cellular PK profile of tisagenelecleucel
qPCR and flow cytometry to measure tisagenlecleucel transgene concentration in blood, bone marrow and other matrices/tissues.
Time frame: Up to Month 60
Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS
Concentration of Tocilizumab
Time frame: Up to Day 7 after tocilizumab infusion
Serum cytokines (IL-10, interferon gamma, IL-6, CRP and ferritin)
Concentration of soluble factors (IL-10, interferon gamma, IL-6, CRP and ferritin) will be listed and summarized by participant and time point.
Time frame: Up to Month 60