B-Cell Non Hodgkin Lymphoma MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: ARI-0001
Product Code: ARI-0001
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: ARI-0001
Other descriptive name: Autologous T cells transduced with lentiviral vector ex
Sponsors
UMCG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed DLBCL and associated subtypes, defined by WHO 2016 classification: DLBCL not otherwise specified (NOS), High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B, T-cell/histocyte rich B-cell lymphoma, Primary mediastinal B-cell lymphoma, EBV+ DLBCL, transformed lymphoma (transformed follicular) and R/R after at least 2 lines of systemic therapy • Age = 18 years • Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0-2 • Secondary central nervous system (CNS) involvement is allowed however, then he/she must have: - No signs or symptoms of CNS involvement that would hamper adequate ICANS assessment • Estimated life expectancy of >3 months other than primary disease • Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen • Signed and dated informed consent before conduct of any trial-specific procedure • Patient is capable of giving informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: • Absolute neutrophil count (ANC) 5 x institutional ULN, unless directly attributable to the lymphoma or Gilbert disease • GFR <40 mL/min calculated according to the modified formula of Cockcroft and Gault or by direct urine collection • Pregnant or breast-feeding woman • Active other malignancy requiring treatment • Medical condition requiring prolonged use of systemic immunosuppressives with exception of prednisolon<10mg/day • History of severe immediate hypersensitivity reaction against any drug or its Ingredients/ impurities that is scheduled to be given during trial participation e.g. as part of the mandatory lymphodepletion protocol, premedication for infusion, or rescue medication/salvage therapies for treatment related toxicities • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare progression free survival (PFS) of patients randomized to investigational point-of-care (PoC) ARI-0001 CAR T-cells versus PFS of patients randomized to commercial standard-of-care (SoC) (axicabtagene ciloleucel (Axi cel, Yescarta)) CAR T-cells inpatients with R/R DLBCL. ;Secondary Objective: • To evaluate response rates • To evaluate safety and toxicity of ARI-0001 and Axi-cel • To assess overall survival • To evaluate quality of life • To assess costs associated with both treatment regimens (ARI-0001 vs Axi-cel) • To evaluate CAR T-cell expansion, persistence, and T-cell characteristics in both treatment arms (ARI-0001 vs Axi-cel) • To evaluate PoC CAR T-cell production characteristics (e.g. number of viable T-cells, transduction efficiency, T-cell subsets (activated T-cells, memory T-cells)), including the functional characteristics between the different production sites. • To evaluate the association of the functional characteristics of ARI-0001 CAR T-cells with CAR T-cell expansion, persistence, adverse events, response rates and PFS. • To assess the proportion of successful batches between the different production sites • To evaluate the number of days between leukapheresis and infusion of CAR T-cells • To evaluate fludarabine pharmacokinetics.;Primary end point(s): • PFS from date of IMP infusion (if applicable);Timepoint(s) of evaluation of this end point: When applicable data of evaluable patients are available | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PFS from date of randomization • Safety and toxicity assessment of ARI-0001 CAR T-cells and Axi-cel per AE reporting classified according to CTCAE Version 5 and CRS and ICANS classified according to the ASTCT criteria • Overall response rate (ORR, sum of (metabolic) complete response [CR] and partial response [PR]), as well as CR, PR, stable disease (SD) and progressive disease (PD)/relapse at 4 weeks, 12 weeks, 6, 12 and 24 months after infusion of CAR T-cells • Best overall response (BOR) rate at 4 weeks, 12 weeks, 6, 12 and 24 months after infusion of CAR T-cells • Duration of response (DOR) • OS from date of randomization, and from date of CAR T-cell infusion (if applicable) • Patient Reported Outcome/Quality of Life (PRO/QOL) • CAR T-cell expansion, persistence, and T-cell characteristics in both treatment arms (ARI-0001 vs Axi-cel) • PoC CAR T-cell production characteristics (e.g. number of viable T-cells, transduction efficiency, T-cell subsets (activated T-cells, memory T-cells)), including the functional characteristics (eg potency tests) between the different production sites. • The association of the functional characteristics (eg potency tests) of the CAR T-cell products (ARI-0001 CAR T-cells) with CAR T-cell expansion, persistence, adverse events, response rates and progression free survival. • Proportion of successful batches between the different production sites • Number of days between leukapheresis and infusion of CAR T-cells (vein-to-vein time) • Fludarabine pharmacokinetics.;Timepoint(s) of evaluation of this end point: When applicable data of evaluable patients are available | — |
Countries
Netherlands
Contacts
Public ContactHOVON
Erasmus MC, HOVON
Outcome results
None listed