Clinical trial NCT04071366: A Study of Itacitinib for the Prevention of Cytokine Release Syndrome Induced by Immune Effector Cell Therapy
Official title: A Phase 2 Study of Itacitinib, for the Prevention of Cytokine Release Syndrome Induced by Immune Effector Cell Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytokine Release Syndrome
Keywords: Cytokine release syndrome
immune effector cell-associated neurotoxicity syndrome
Janus kinase inhibitor
immune effector cell therapy
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2019-08-28
Enrollment: 112
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1: Singe Group Assignment Part 2: Parallel Assignment
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: up to Day 14 of Parts 1 and 2
Secondary outcomes:
measure: Percentage of Participants With Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) by Day 28 After IEC Therapy, Assessed by Using the ICANS Consensus Grading
timeFrame: up to Day 28 of Parts 1 and 2
measure: Time to Onset of ICANS Using the ICANS Consensus Grading, Regardless of CRS, by Day 28 After IEC Therapy
timeFrame: up to Day 28 of Parts 1 and 2
measure: Duration of ICANS Occurring by Day 28 After IEC Therapy Using the ICANS Consensus Grading, Regardless of CRS
timeFrame: up to Day 28 of Parts 1 and 2
measure: Time to Onset of All Grades of CRS by Day 28 After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading
timeFrame: up to Day 28 of Parts 1 and 2
measure: Duration of All Grades of CRS Occurring by Day 28 After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading
timeFrame: up to Day 56 of Parts 1 and 2
measure: Percentage of Participants With Any Grade of CRS at 48 Hours After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading
timeFrame: up to Day 2 of Parts 1 and 2
measure: Percentage of Participants With ≥Grade 2 CRS by Day 28 After First IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading
timeFrame: up to Day 28 of Parts 1 and 2
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Except CRS and ICANS
timeFrame: from at Day -3 through the duration of safety follow-up (up to Day 56) for Parts 1 and 2
measure: Percentage of Participants With Any ≥Grade 3 Cytopenias Ongoing at Day 28
timeFrame: Day 28 of Parts 1 and 2
measure: Percentage of Participants Who Were Treated With Tocilizumab for CRS
timeFrame: up to Day 56 of Parts 1 and 2
measure: Percentage of Participants Requiring More Than 1 Dose of Dexamethasone (or Equivalent) for ICANS
timeFrame: up to Day 30 of Parts 1 and 2
Other outcomes:
measure: Number of Hospital Admissions for Participants With CRS and/or ICANS by the End of the Study
timeFrame: up to Day 180 of Parts 1 and 2
measure: Duration of Hospital Stay for Participants With CRS and/or ICANS by End of Study
timeFrame: up to Day 180 of Parts 1 and 2
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Incyte Corporation
name: Peter Langmuir, MD
role: STUDY_DIRECTOR
References:
citation: Huarte E, O'Connor RS, Peel MT, Nunez-Cruz S, Leferovich J, Juvekar A, Yang YO, Truong L, Huang T, Naim A, Milone MC, Smith PA. Itacitinib (INCB039110), a JAK1 Inhibitor, Reduces Cytokines Associated with Cytokine Release Syndrome Induced by CAR T-cell Therapy. Clin Cancer Res. 2020 Dec 1;26(23):6299-6309. doi: 10.1158/1078-0432.CCR-20-1739. Epub 2020 Sep 30.