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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Hematological Malignancy
• Intervention / Treatment: Drug: Metoprolol; Drug: metoprolol, infliximab, etanercept, tocilizumab and/or other agents

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Weidong Han, M.D.; Phone Number: +861066939711; Email: hanwdrsw@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Biotherapeutic Department of Chinese PLA General Hospital
      • Contact: Weidong Han, M.D; Phone Number: +861066939711; Email: hanwdrsw@sina.com
      • Contact: Qingming Yang, M.D; Phone Number: +861066939460; Email: yangqm@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conditional therapy mode group; 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; Metoprolol was given in patients who received CAR T cell therapy for CRS control or CRS precaution.; Drug: metoprolol, infliximab, etanercept, tocilizumab and/or other agents; 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.
Experimental: Prophylactic therapy mode group; 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; Metoprolol was given in patients who received CAR T cell therapy for CRS control or CRS precaution.; Drug: metoprolol, infliximab, etanercept, tocilizumab and/or other agents; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of metoprolol for CRS control	Reduction of Body temperature in degree centigrade	2-4 weeks
Efficacy of metoprolol for CRS precaution	Reduction of serum IL-6 in pg/dl.	2-4 weeks

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2019
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: cytokine release syndrome; Metoprolol; chimeric antigen receptor T cells
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Shock; Hematologic Neoplasms; Cytokine Release Syndrome; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Etanercept; Infliximab; Metoprolol
• Other Study ID Numbers: CHN-PLAGH-BT-044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No