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

NCT06430736 | Recruiting Phase 2

• 1 other identifier: PRONTO
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myeloma; Lymphoma; Leukemia

Keywords

Tocilizumab; Myeloma; Leukemia; Lymphoma; CRS; ICANS

Outcome Measures

Primary Outcomes (1)

• Incidence of CRS of all grades

  Number of patients with CRS of any grade according to the ASTCT (American Society for Transplantation and Cellular Therapy ) Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells ; including use of antipyretics

  30 days

Secondary Outcomes (10)

• Incidence of ICANS of all grades

  30 days

• Hospitalization duration

  30 days

• Erythrocyte transfusion needs

  90 days

• Platelet transfusion needs

  90 days

• Incidence of admissions to the intensive care unit

  30 days

Study Arms (2)

Tocilizumab prophylactic

EXPERIMENTAL

In the experimental arm, patients will receive a single standard dose of Tocilizumab (Actemra®) 8 mg/kg b.w. intravenously infused over 1 hour in 250 ml NaCl 0.9%, with completion of the infusion 1 hour prior to the infusion of the CAR-T cells. Prior to Tocilizumab administration, no specific premedication is given. The treatment of eventual subsequent CRS will be identical as in patients in the standard arm.

Drug: Tocilizumab before CAR-T cell infusion

Tocilizumab on demand

ACTIVE COMPARATOR

In the standard arm, patients will receive conventional antipyretics and Tocilizumab at first clinical signs (being grade 1 or higher) of emerging CRS. Tocilizumab will be given at the standard-dose of 8 mg/kg b.w. intravenously over one hour in 250 ml NaCl 0.9%, and it will be repeated after 8 hours for a maximum of four administrations in patients with ongoing signs of CRS. Prior to Tocilizumab administration, no specific premedication is given.

Drug: Tocilizumab at emerging CRS

Interventions

Tocilizumab before CAR-T cell infusion DRUG

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.

Also known as: Prophylactic

Tocilizumab prophylactic

Tocilizumab at emerging CRS DRUG

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.

Also known as: On demand

Tocilizumab on demand

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Insel Gruppe AG

Bern, Canton of Bern, 3010, Switzerland

RECRUITING

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Lymphoma; Leukemia

Interventions

Abortion, Legal

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Abortion, Induced; Obstetric Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Thomas Pabst, Prof.

  Insel Gruppe AG Bern Switzerland

  STUDY CHAIR

Central Study Contacts

Thomas Pabst, Prof.

CONTACT

+41 31 632 84 30; thomas.pabst@insel.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, two arm, open-label, single-center trial.

Study Record Dates

• First Submitted: May 21, 2024
• First Posted: May 28, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 8, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 24 months
• Access Criteria: email contact: thomas.pabst@insel.ch

Locations

CH (1)