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

Study Overview
=================
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.

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

Conditions
-----------------
Solid Tumor, Hematological Malignancy

Intervention / Treatment
-----------------
* Drug: Metoprolol
* Drug: metoprolol, infliximab, etanercept, tocilizumab and/or other agents


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metoprolol, cytokine release syndrome, chimeric antigen receptor T cells