Metoprolol Treatment for Cytokine Release Syndrome in Patients Treated With Chimeric Antigen Receptor T Cells

NCT04082910 | Unknown Phase 1 DMC

• 1 other identifier: CHN-PLAGH-BT-044
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this prospective study is to evaluate the feasibility and efficacy of metoprolol, a beta-1 adrenergic receptor blocker, in the treatment of cytokine release syndrome (CRS) caused by chimeric antigen receptor T (CAR T) cell infusions, its effects on the serum levels of Interleukin-6 (IL-6) and other cytokines.

Conditions

Solid Tumor; Hematological Malignancy

Keywords

Metoprolol; cytokine release syndrome; chimeric antigen receptor T cells

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of metoprolol in patients treated by CAR T infusions.

  Reduction of heart rate in bpm (beats per minute)

  2-4 weeks

• Safety and tolerability of metoprolol in patients treated by CAR T infusions.

  Reduction of blood pressure in mmHg

  2-4 weeks

Secondary Outcomes (2)

• Efficacy of metoprolol for CRS control

  2-4 weeks

• Efficacy of metoprolol for CRS precaution

  2-4 weeks

Study Arms (2)

Conditional therapy mode group

EXPERIMENTAL

Metoprolol (12.5-25 mg per dose, every 12 hours) was initially given from the day of CRS diagnosis confirmation post CAR T cell infusions till CRS remission in patients without bulky tumor burden. For all metoprolol-treated patients, the use of antibodies (infliximab, etanercept and tocilizumab) and/or other agents were not completely limited under the consideration of clinical requirement for sufficient control of continuously progressed CRS.

Drug: Metoprolol; Drug: metoprolol, infliximab, etanercept, tocilizumab and/or other agents

Prophylactic therapy mode group

EXPERIMENTAL

Metoprolol (12.5-25 mg per dose, every 12 hours) was given starting from the day before CAR T infusion till CRS remission in patients with bulky disease. For all metoprolol-treated patients, the use of antibodies (infliximab, etanercept and tocilizumab) and/or other agents were not completely limited under the consideration of clinical requirement for sufficient control of continuously progressed CRS.

Drug: Metoprolol; Drug: metoprolol, infliximab, etanercept, tocilizumab and/or other agents

Interventions

Metoprolol DRUG

Metoprolol was given in patients who received CAR T cell therapy for CRS control or CRS precaution.

Conditional therapy mode group; Prophylactic therapy mode group

metoprolol, infliximab, etanercept, tocilizumab and/or other agents DRUG

During the term of metoprolol use, antibodies (infliximab, etanercept and tocilizumab) and/or other agents were not completely limited to be used under the consideration of clinical requirement for sufficient control of continuously progressed CRS.

Conditional therapy mode group; Prophylactic therapy mode group

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with lymphoma, leukemia or other malignant diseases who were enrolled for CAR T cell therapy.

You may not qualify if:

• Patients with contraindications indicated in metoprolol instruction, including:
• Significant bradycardia (heart rate \< 45/min)
• Cardiogenic shock
• Severe or acute heart failure
• Poor peripheral circulation perfusion
• Grade II or III atrioventricular block
• Sick sinus syndrome
• Severe peripheral vascular disease

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms; Cytokine Release Syndrome

Interventions

Metoprolol; Infliximab; Etanercept

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Central Study Contacts

Weidong Han, M.D.

CONTACT

+861066939711; hanwdrsw@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 4, 2019
• First Posted: September 10, 2019
• Study Start: September 15, 2019
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2023
• Last Updated: April 13, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)