Adult patients with refractory or relapsed follicular lymphoma MedDRA version: 20.0 Level: HLT Classification code 10016903 Term: Follicle centre lymphomas, follicular grade I, II, III System Organ Class: 100000004851 MedDRA version: 21.1 Level: PT Classification code 10061170 Term: Follicle centre lymphoma, follicular grade I, II, III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Written informed consent prior to any screening procedures •=18 years of age at the time of ICF signature •FL (Grade 1, 2, 3A) confirmed histologically by central pathology review before tisagenlecleucel infusion. •FL meeting one of the following criteria: oRefractory to a second line or later line of systemic therapy (including anti-CD20 antibodies and alkylating agents) or relapsed within 6 months after completion of a second line or later line of systemic therapy oRelapsed during anti-CD20 antibody maintenance (following at least two lines of therapies as above) or within 6 months after maintenance completion oRelapsed after autologous HSCT •Radiographically measurable disease at screening defined as: •At least one nodal lesion greater than 20 mm in the long axis, regardless of the length of the short axis AND/OR •Extranodal lesions (outside lymph node or nodal mass, including liver and spleen) greater than 10 mm in long AND short axis Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 23
Exclusion criteria
Exclusion criteria: •Evidence of histologic transformation •Follicular Lymphoma Grade 3B •Prior anti-CD19 therapy •Prior gene therapy •Prior adoptive T cell therapy •Prior allogeneic hematopoietic stem cell transplant •Active CNS involvement by malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of tisagenlecleucel therapy as measured by CRR determined by IRC;Secondary Objective: - Evaluate the efficacy of tisagenlecleucel as measured by additional efficacy measures, including ORR, DOR, PFS and OS - Evaluate safety of tisagenlecleucel - Characterize the in vivo cellular kinetics (levels, expansion, persistence) of tisagenlecleucel transduced cells into target tissues (blood, bone marrow, and other tissues if available) and CD3+ tisagenlecleucel cells in peripheral blood, summarized by clinical response - Characterize the incidence and prevalence of tisagenlecleucel immunogenicity (humoral and cellular) - Characterize the impact of pre-existing and treatment induced immunogenicity (cellular and humoral) on cellular kinetics, efficacy and safety - Describe the effect of tisagenlecleucel therapy on Patient reported outcomes (PRO) ;Primary end point(s): Complete response rate (CRR) determined by an Independent Review Committee (IRC) in the efficacy analysis set (EAS) based on Lugano 2014 classification response criteria (Cheson et al 2014). ;Timepoint(s) of evaluation of this end point: When approximately 50 patients have received treatment and have either completed 6 months from study day 1 infusion or discontinued earlier; when 90 patients have received treatment and have either completed 6 months from study day 1 infusion or discontinued earlier. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - ORR, including complete response (CR) and partial response (PR) determined by IRC in the FAS based on Lugano 2014 classification. - DOR, defined as time from achievement of CR or PR to relapse or death due to FL, based on IRC - DOR for CR only, defined as time from achievement of CR to relapse or death due to FL, based on IRC - PFS, defined as time from tisagenlecleucel infusion to first documented disease progression or death due to any cause, based on IRC - OS, defined as time from tisagenlecleucel infusion to death due to any cause - Type, frequency and severity of adverse events and laboratory abnormalities - Summary of qPCR detected tisagenlecleucel transgene concentrations in peripheral blood, bone marrow and other tissues by time point and clinical response status - Summary of cellular kinetic parameters: Cmax, Tmax, AUC0-28 and AUC0-84d, T1/2, and/or other relevant parameters in peripheral blood; bone marrow and other tissues by clinical response as appropriate - Summary of exposure and cellular kinetic parameters of CD3+ tisagenlecleucel cells in peripheral blood detected by flow cytometry - Summary of pre-existing and treatment induced immunogenicity (cellular and humoral) of tisagenlecleucel - Levels of pre-existing and treatment induced immunogenicity - Cellular kinetic parameters (Cmax, AUCs, Tlast), concentration-time profile tisagenlecleucel by immunogenicity category (positive/negative) - Efficacy (ORR, DOR, PFS) - Safety (B-cell levels, CRS grades, neurologic events) - Summary scores of PRO measured by SF-36 version 2, EQ-5D-3L and FACT-Lym quality of life questionnaires;Timepoint(s) of evaluation of this end point: When approximately 50 patients have received treatment and have either completed 6 months from study day 1 infusion or discontinued earlier; when 90 patients have received treatment and have either completed 6 months from study day 1 infusion or discontinued earlier; the end of the study (Part | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Japan, Netherlands, Norway, Spain, United Kingdom, United States
Contacts
Public ContactDrug Regulatory Affairs
Novartis Pharma GmbH
Outcome results
None listed