Diffuse Large B-Cell Lymphoma (DLBCL)
Conditions
Keywords
Diffuse Large B-cell Lymphoma, double/triple hit lymphoma, relapsed/refractory, tisagenlecleucel, CTL019, Chinese
Brief summary
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.
Detailed description
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).
Interventions
BIOLOGICALTisagenlecleucel
A single intravenous (i.v.) infusion of 0.6 - 6.0×10\^8 CAR positive viable T cells.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study 2. Patients must be ≥18 years of age at the time of ICF signature 3. Histologically confirmed DLBCL at last relapse (including DLBCL transformed from follicular lymphoma and double-triple hit lymphoma) 4. Relapsed or refractory disease after at least 2 lines of systemic therapy, including anti-CD20 antibody and an anthracycline, or having failed or being ineligible for autologous HSCT 5. ECOG performance status that is either 0 or 1 at screening 6. Measurable disease at time of enrollment: * Nodal lesions greater than 15 mm in the long axis, regardless of the length of the short axis or * Extra nodal lesion (outside lymph node or nodal mass, but including liver and spleen) at least 10 mm in long and short axis 7. Adequate organ function 8. Must have a leukapheresis material of non-mobilized cells available for manufacturing
Exclusion criteria
1. Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene therapy product 2. Primary mediastinal large B-cell lymphoma, EBV+ DLBCL, Richter's transformation, Burkitt lymphoma, primary DLBCL of CNS, T cell / histiocyte rich large B-cell lymphoma, primary cutaneous DLBCL. 3. Eligible for and consenting to autologous HSCT 4. Prior allogeneic SCT 5. Active CNS involvement by disease under study, except if the CNS involvement has been effectively treated (i.e. patient is asymptomatic) and local treatment was greater than 4 weeks before enrollment 6. Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome) 7. Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | Complete Response (CR) and Partial Response (PR) according to the Lugano classification as determined by the Investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | Time from CR or PR, whichever occurs first, to relapse or death due to DLBCL. |
| Time to response (TTR) | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | Time from tisagenlecleucel infusion to CR or PR, whichever occurs first. |
| Progression-Free Survival (PFS) | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | Time from tisagenlecleucel infusion to the first documented disease progression or death due to any cause. |
| Event free survival (EFS) | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | Time from tisagenlecleucel infusion to the first documented disease progression or relapse, new treatment for lymphoma or death due to any cause. |
| Overall Survival (OS) | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | Time from tisagenlecleucel infusion to death due to any cause. |
| Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | 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. |
| Tisagenlecleucel immunogenicity (humoral) | Up to Month 60 | The humoral immunogenicity assay will be evaluated to measure the antibody titers specific to the tisagenlecleucel molecule prior to and following infusion. |
| Tisagenlecleucel immunogenicity (cellular) | Up to Month 60 | The cellular immunogenicity assay will be evaluated to assess the presence of T lymphocytes activated by the tisagenlecleucel protein. |
| In vivo cellular PK profile of tisagenelecleucel | Up to Month 60 | qPCR and flow cytometry to measure tisagenlecleucel transgene concentration in blood, bone marrow and other matrices/tissues. |
| Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS | Up to Day 7 after tocilizumab infusion | Concentration of Tocilizumab |
| Serum cytokines (IL-10, interferon gamma, IL-6, CRP and ferritin) | Up to Month 60 | Concentration of soluble factors (IL-10, interferon gamma, IL-6, CRP and ferritin) will be listed and summarized by participant and time point. |
Outcome results
None listed