RecruitingPhase 2NCT06430736

PRONTO Trial (PRophylactic Versus ON-demand Use of TOcilizumab)

Prospective Comparison Between Prophylactic and On-demand Use of Tocilizumab in CAR-T Recipients - a Randomized, Two Arm, Open-label, Single-center Trial

Sponsor

Insel Gruppe AG, University Hospital Bern

Enrollment

100 participants

Start Date

Jul 1, 2024

Study Type

INTERVENTIONAL

Conditions

Lymphoma Leukemia Myeloma

Summary

Despite the consequent use of Tocilizumab together with conventional antipyretics at early/first 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.

Eligibility

Min Age: 18 Years

Inclusion Criteria4

Patients planned to receive commercial CAR-T treatment for all registered indications comprising lymphomas, leukemias or myeloma at a single academic center (Bern Inselspital)
With written informed consent
Considered by the investigator to be clinically fit for this treatment
Patients aged ≥18 years

Exclusion Criteria6

Previous Tocilizumab treatment within 3 months prior to CAR-T infusion
Patients with treatment with an investigational compound within 8 weeks prior to CAR-T infusion
Women who are pregnant or breast feeding, or women intending to become pregnant during the study period; or participants lacking safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases during study treatment and for a total of 12 months; Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
Previous enrolment into the current study
Enrolment of the investigator, his/her family members, employees and other dependent persons

Interventions

DRUGTocilizumab before CAR-T cell infusion

Tocilizumab will be given at the standard-dose of 8 mg/kg b.w. intravenously, with completion of the infusion 1 hour prior to infusion of CAR-T cells. Treatment of eventual subsequent CRS/ICANS will be identical as in patients in the standard arm.

DRUGTocilizumab at emerging CRS

Tocilizumab will be given at the standard-dose of 8 mg/kg b.w. intravenously, and it will be repeated after 8 hours for a maximum of four administrations in patients with ongoing signs of CRS.