A Study of Itacitinib for the Prevention of Cytokine Release Syndrome Induced by Immune Effector Cell Therapy

Cytokine Release Syndrome Clinical Trial

Official title:

A Phase 2 Study of Itacitinib, for the Prevention of Cytokine Release Syndrome Induced by Immune Effector Cell Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04071366
• Other study ID #: INCB 39110-211
• Status: Completed
• Phase: Phase 2
• Start date: February 7, 2020
• Est. completion date: August 22, 2023

Study information

• Verified date: February 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

"The purpose of this study is to assess the safety and efficacy of oral administration of itacitinib for the prevention of cytokine release syndrome (CRS) in male or female participants aged 12 years or older and who are planning to receive an approved immune effector cell (IEC) therapy for hematologic malignancies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: August 22, 2023
• Est. primary completion date: February 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Part 1: Eligible to receive any IEC therapy for any approved indication.
• Part 2: Eligible to receive Yescarta for relapsed or refractory large B-cell lymphoma or follicular lymphoma.
• Eastern Cooperative Oncology Group performance status 0 to 1.
• Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

• Evidence of active uncontrolled/untreated infection (viral, bacterial, fungal, opportunistic) of any origin.
• Evidence of active hepatitis B virus or hepatitis C virus infection.
• Known human immunodeficiency virus.
• Active acute or chronic graft-versus-host disease requiring systemic therapy.
• Concurrent use of chronic systemic steroids or immunosuppressant medications.
• Any unresolved toxicity = Grade 2 (except stable Grade 2 peripheral neuropathy or alopecia) from previous anticancer therapy.
• Known history or prior diagnosis of immunologic or inflammatory/autoimmune disease affecting the central nervous system (CNS) and unrelated to their disease under study or previous treatment.
• Clinically significant or uncontrolled cardiac disease.
• Acute lymphoblastic leukemia participants with protocol-defined CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia.
• Diffuse large B-cell lymphoma participants must have no signs or symptoms of CNS disease or detectable evidence of CNS disease; participants who have been previously treated for CNS disease but have no evidence of disease at screening are eligible.
• Laboratory values at screening outside the protocol-defined ranges.

Related Conditions & MeSH terms

• Cytokine Release Syndrome
• Syndrome

Intervention

Drug:
• Itacitinib
Part 1: Itacitinib 200 mg once daily for 30 days. Part 2: Itacitinib 200 mg twice daily for 30 days.
• Immune effector cell therapy
Participants will receive IEC therapy that is approved by the health authority in the country where the study is being conducted for any approved hematologic indication.
• Placebo
Participants will receive placebo twice daily.

Biological:
• Yescarta
Eligible participants are receiving Yescarta (An infusion of chimeric antigen receptor (CAR)-transduced autologous T cells) for relapsed or refractory larbe B-cell lymphoma or follicular lymphoma intravenously.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Hospital Admissions for Participants With CRS and/or ICANS by the End of the Study	The number of hospital admissions was assessed through study completion.	up to Day 180 of Parts 1 and 2
Other	Duration of Hospital Stay for Participants With CRS and/or ICANS by End of Study	The duration of hospital stays was assessed through study completion.	up to Day 180 of Parts 1 and 2
Primary	Percentage of Participants Who Developed =Grade 2 Cytokine Release Syndrome (CRS) by Day 14 After Immune Effector Cell (IEC) Therapy, Assessed by Using American Society for Blood and Marrow Transplantation (ASBMT) CRS Consensus Grading	The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 2 CRS: temperature =38°C not attributable to any other cause, defined as fever; hypotension not requiring vasopressors, and/or; hypoxia requiring low-flow nasal cannula (oxygen delivered at =6 liters/minute) or blow-by. Grade 3 CRS: fever; hypotension requiring one vasopressor with or without vasopressin, and/or; hypoxyia requiring high-flow nasal cannula (oxygen delivered at >6 liters/minute), facemask, nonrebreather mask, or Venturi mask. Grade 4 CRS: fever; hypotension requiring multiple vasopressors (excluding vasopressin), and/or; hypoxia requiring positive pressure (e.g., continuous positive airway pressure [CPAP], bilevel intermittent positive air pressure [BiPAP], intubation, mechanical ventilation).	up to Day 14 of Parts 1 and 2
Secondary	Percentage of Participants With Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) by Day 28 After IEC Therapy, Assessed by Using the ICANS Consensus Grading	Participants were monitored for signs and symptoms of ICANS, if symptoms developed at any point after IEC. ICANS Consensus Grading Criteria were used to assess 5 domains of neurotoxicity: orientation (orient to year, month, city, and hospital), naming (naming 3 objects), following commands (follow commands such as: show me 2 fingers or close your eyes and stick out your tongue), writing (ability to write a standard sentence), and attention (count backwards from 100 by 10). Each domain is associated with a certain number of points, which are summed to generate a total score. Score 10: no impairment; score 7-9: Grade 1 ICANS; score 3-6: Grade 2 ICANS; score 0-2: Grade 3 ICANS.	up to Day 28 of Parts 1 and 2
Secondary	Time to Onset of ICANS Using the ICANS Consensus Grading, Regardless of CRS, by Day 28 After IEC Therapy	Participants were monitored for signs and symptoms of ICANS, if symptoms developed at any point after IEC. ICANS Consensus Grading Criteria were used to assess 5 domains of neurotoxicity: orientation (orient to year, month, city, and hospital), naming (naming 3 objects), following commands (follow commands such as: show me 2 fingers or close your eyes and stick out your tongue), writing (ability to write a standard sentence), and attention (count backwards from 100 by 10). Each domain is associated with a certain number of points, which are summed to generate a total score. Score 10: no impairment; score 7-9: Grade 1 ICANS; score 3-6: Grade 2 ICANS; score 0-2: Grade 3 ICANS.	up to Day 28 of Parts 1 and 2
Secondary	Duration of ICANS Occurring by Day 28 After IEC Therapy Using the ICANS Consensus Grading, Regardless of CRS	Participants were monitored for signs and symptoms of ICANS, if symptoms developed at any point after IEC. ICANS Consensus Grading Criteria were used to assess 5 domains of neurotoxicity: orientation (orient to year, month, city, and hospital), naming (naming 3 objects), following commands (follow commands such as: show me 2 fingers or close your eyes and stick out your tongue), writing (ability to write a standard sentence), and attention (count backwards from 100 by 10). Each domain is associated with a certain number of points, which are summed to generate a total score. Score 10: no impairment; score 7-9: Grade 1 ICANS; score 3-6: Grade 2 ICANS; score 0-2: Grade 3 ICANS. Duration of ICANS occurring by Day 28 corresponds to the sum of days with non-zero grade ICANS by Day 28.	up to Day 28 of Parts 1 and 2
Secondary	Time to Onset of All Grades of CRS by Day 28 After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading	The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 1: fever; either no hypotention and/or no hypoxia. Grade 2 CRS: fever; hypotension not requiring vasopressors, and/or; hypoxia requiring low-flow nasal cannula (oxygen delivered at =6 liters/minute) or blow-by. Grade 3 CRS: fever; hypotension requiring one vasopressor with or without vasopressinc, and/or; hypoxyia requiring high-flow nasal cannula (oxygen delivered at >6 liters/minute), facemask, nonrebreather mask, or Venturi mask. Grade 4 CRS: fever; hypotension requiring multiple vasopressors (excluding vasopressin), and/or; hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, mechanical ventilation).	up to Day 28 of Parts 1 and 2
Secondary	Duration of All Grades of CRS Occurring by Day 28 After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading	The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 1: fever; either no hypotention and/or no hypoxia. Grade 2 CRS: fever; hypotension not requiring vasopressors, and/or; hypoxia requiring low-flow nasal cannula (oxygen delivered at =6 liters/minute) or blow-by. Grade 3 CRS: fever; hypotension requiring one vasopressor with or without vasopressinc, and/or; hypoxyia requiring high-flow nasal cannula (oxygen delivered at >6 liters/minute), facemask, nonrebreather mask, or Venturi mask. Grade 4 CRS: fever; hypotension requiring multiple vasopressors (excluding vasopressin), and/or; hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, mechanical ventilation).	up to Day 56 of Parts 1 and 2
Secondary	Percentage of Participants With Any Grade of CRS at 48 Hours After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading	The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 1: fever; either no hypotention and/or no hypoxia. Grade 2 CRS: fever; hypotension not requiring vasopressors, and/or; hypoxia requiring low-flow nasal cannula (oxygen delivered at =6 liters/minute) or blow-by. Grade 3 CRS: fever; hypotension requiring one vasopressor with or without vasopressinc, and/or; hypoxyia requiring high-flow nasal cannula (oxygen delivered at >6 liters/minute), facemask, nonrebreather mask, or Venturi mask. Grade 4 CRS: fever; hypotension requiring multiple vasopressors (excluding vasopressin), and/or; hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, mechanical ventilation).	up to Day 2 of Parts 1 and 2
Secondary	Percentage of Participants With =Grade 2 CRS by Day 28 After First IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading	The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 1: fever; either no hypotention and/or no hypoxia. Grade 2 CRS: fever; hypotension not requiring vasopressors, and/or; hypoxia requiring low-flow nasal cannula (oxygen delivered at =6 liters/minute) or blow-by. Grade 3 CRS: fever; hypotension requiring one vasopressor with or without vasopressinc, and/or; hypoxyia requiring high-flow nasal cannula (oxygen delivered at >6 liters/minute), facemask, nonrebreather mask, or Venturi mask. Grade 4 CRS: fever; hypotension requiring multiple vasopressors (excluding vasopressin), and/or; hypoxia requiring positive pressure (e.g., CPAP, BiPAP, intubation, mechanical ventilation).	up to Day 28 of Parts 1 and 2
Secondary	Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Except CRS and ICANS	An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. For purposes of analysis, all AEs were considered TEAEs unless the AE could unequivocally be defined as not treatment emergent.	from at Day -3 through the duration of safety follow-up (up to Day 56) for Parts 1 and 2
Secondary	Percentage of Participants With Any =Grade 3 Cytopenias Ongoing at Day 28	Cytopenia is characterized by low levels of white blood cells, red blood cells, or platelets. Analysis used laboratory counts at Day 28.	Day 28 of Parts 1 and 2
Secondary	Percentage of Participants Who Were Treated With Tocilizumab for CRS	Tocilizumab and/or corticosteroids for CRS Grade 1 was not allowed per the protocol. However, tocilizumab may have been given as rescue medication for CRS Grade 1 if no improvement was observed within 72 hours from onset, and the participant's medical condition required intervention per investigator judgment.	up to Day 56 of Parts 1 and 2
Secondary	Percentage of Participants Requiring More Than 1 Dose of Dexamethasone (or Equivalent) for ICANS	Dexamethasone use as rescue medication for ICANS was assessed.	up to Day 30 of Parts 1 and 2