Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06430736
Status:
RECRUITING
Last Update Posted:
2024-07-08
First Post:
2024-05-21
Brief Title:
PRONTO Trial PRophylactic Versus ON-demand Use of TOcilizumab
Sponsor:
Insel Gruppe AG University Hospital Bern
Organization:
Insel Gruppe AG University Hospital Bern
Study Overview
Official Title:
Prospective Comparison Between Prophylactic and On-demand Use of Tocilizumab in CAR-T Recipients - a Randomized Two Arm Open-label Single-center Trial
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRONTO
Brief Summary:
Despite the consequent use of Tocilizumab together with conventional antipyretics at earlyfirst signs of emerging CRS CRS and eventually the subsequent development of ICANS remain a major concern for patients
This study aims to identify safety and efficacy of prophylactic Tocilizumab treatment In particular to explore whether prophylactic Tocilizumab treatment can decrease the incidence and severity of CRS and subsequent eventual neurotoxicity following CAR-T-treatment
This study aims to identify safety and efficacy of prophylactic Tocilizumab treatment In particular to explore whether prophylactic Tocilizumab treatment can decrease the incidence and severity of CRS and subsequent eventual neurotoxicity following CAR-T-treatment
Detailed Description:
Adoptive immunotherapy with CD19 cluster of differentiation antigen 19 targeting chimeric antigen-receptor CAR-T cells is an effective therapeutic strategy against relapsed or refractory B-cell malignancies including B-cell lymphomas B-ALL acute lymphoblastic leukemia and myeloma Currently up to 50 commercial CAR-T-cell treatments are performed annually at the Inselspital in Bern making it by far the largest center for CAR-T cell treatment in Switzerland
CAR-T treatment is associated with well-described acute adverse events including cytokine release syndrome CRS and neurotoxicity termed immune effector cell associated neurologic syndrome ICANS CRS at all grades occurs in between 42 to 93 of all patients with variations among available products and ICANS can occur at all grades in 21 up to 64
Acute complications of CAR-T cell therapy are the result of rapid CAR-T cell expansion and of a hyper-inflammatory state related to cell activation Interleukin IL-6 is a central mediator of cytokine-responses in CRS and ICANS together with other cytokines and chemokines involved IL-6 interacts with its receptor IL-6R in either membrane-bound form leading to classic IL-6 signaling after interacting with GP130 or soluble in plasma where the IL-6 IL-6R complex interacts with GP130 expressing cells in trans IL-6 signaling
Tocilizumab is a humanized monoclonal antibody that binds the IL-6R in both its soluble and membrane-bound forms Tocilizumab treatment has become the standard of care for patients presenting with CRS at all grades together with antipyretic treatment grades 1 or 2 at the regular ward or with vasoactive andor ventilation support at the intensive care unit grades 3 and 4
The study aims to assess the incidence of CRS of all grades as well as the incidence of ICANS of all grades the duration of hospitalisation and the need of platelet and erythrocyte transfusion within the first three months after CAR-T treatment in patients receiving prophylactic Tocilizumab compared to patients receiving on-demand Tocilizumab
CAR-T treatment is associated with well-described acute adverse events including cytokine release syndrome CRS and neurotoxicity termed immune effector cell associated neurologic syndrome ICANS CRS at all grades occurs in between 42 to 93 of all patients with variations among available products and ICANS can occur at all grades in 21 up to 64
Acute complications of CAR-T cell therapy are the result of rapid CAR-T cell expansion and of a hyper-inflammatory state related to cell activation Interleukin IL-6 is a central mediator of cytokine-responses in CRS and ICANS together with other cytokines and chemokines involved IL-6 interacts with its receptor IL-6R in either membrane-bound form leading to classic IL-6 signaling after interacting with GP130 or soluble in plasma where the IL-6 IL-6R complex interacts with GP130 expressing cells in trans IL-6 signaling
Tocilizumab is a humanized monoclonal antibody that binds the IL-6R in both its soluble and membrane-bound forms Tocilizumab treatment has become the standard of care for patients presenting with CRS at all grades together with antipyretic treatment grades 1 or 2 at the regular ward or with vasoactive andor ventilation support at the intensive care unit grades 3 and 4
The study aims to assess the incidence of CRS of all grades as well as the incidence of ICANS of all grades the duration of hospitalisation and the need of platelet and erythrocyte transfusion within the first three months after CAR-T treatment in patients receiving prophylactic Tocilizumab compared to patients receiving on-demand Tocilizumab
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None