Study of Tisagenlecleucel in Chinese Adult Patients With Relapsed or Refractory Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL)

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase II, Single-arm, Multicenter Trial to Evaluate the Efficacy and Safety of Tisagenlecleucel in Chinese Adult Patients With Relapsed or Refractory Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL)

Conditions
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Diffuse Large B-Cell Lymphoma (DLBCL)

Intervention / Treatment
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* Biological: Tisagenlecleucel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study Patients must be ≥18 years of age at the time of ICF signature Histologically confirmed DLBCL at last relapse (including DLBCL transformed from follicular lymphoma and double-triple hit lymphoma) 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 ECOG performance status that is either 0 or 1 at screening 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 Adequate organ function Must have a leukapheresis material of non-mobilized cells available for manufacturing Exclusion Criteria: Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene therapy product 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. Eligible for and consenting to autologous HSCT Prior allogeneic SCT 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 Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome) Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tisagenlecleucel<br>All patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel. | Biological: Tisagenlecleucel<br>* A single intravenous (i.v.) infusion of 0.6 - 6.0×10^8 CAR positive viable T cells.<br>* Other names: CTL019;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Complete Response (CR) and Partial Response (PR) according to the Lugano classification as determined by the Investigator. | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | Time from CR or PR, whichever occurs first, to relapse or death due to DLBCL. | 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. | 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. | 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. | 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. | From first dosing (single administration, Day 1) up to End of Study Visit (EOS), an average of 60 Months | 
| 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. | 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. | 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. | 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. | Up to Month 60 | 
| Concentration of Tocilizumab PK in tocilizumab treated subjects during CRS | Concentration of Tocilizumab | 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. | Up to Month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diffuse Large B-cell Lymphoma, double/triple hit lymphoma, relapsed/refractory, tisagenlecleucel, CTL019, Chinese