A Phase 2 Study of Itacitinib, for the Prevention of Cytokine Release Syndrome Induced by Immune Effector Cell Therapy
Overview
- Phase
- Phase 2
- Intervention
- Itacitinib
- Conditions
- Cytokine Release Syndrome
- Sponsor
- Incyte Corporation
- Enrollment
- 112
- Locations
- 10
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
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
- •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.
Arms & Interventions
Part 1: Open Label Itacitinib Once Daily
During Part 1, all participants receive itacitinib 200mg once daily (open label) for 30 days. The study population will include participants receiving any approved IEC for an approved indication.
Intervention: Itacitinib
Part 1: Open Label Itacitinib Once Daily
During Part 1, all participants receive itacitinib 200mg once daily (open label) for 30 days. The study population will include participants receiving any approved IEC for an approved indication.
Intervention: Immune effector cell therapy
Part 2: Double-Blind Itacitinib Twice Daily
During Part 2, participants will be randomized to receive itacitinib 200mg or placebo twice daily for 30 days. The study population also includes participants who are receiving Yescarta for relapsed or refractory large B-cell lymphoma or follicular lymphoma.
Intervention: Itacitinib
Part 2: Double-Blind Itacitinib Twice Daily
During Part 2, participants will be randomized to receive itacitinib 200mg or placebo twice daily for 30 days. The study population also includes participants who are receiving Yescarta for relapsed or refractory large B-cell lymphoma or follicular lymphoma.
Intervention: Placebo
Part 2: Double-Blind Itacitinib Twice Daily
During Part 2, participants will be randomized to receive itacitinib 200mg or placebo twice daily for 30 days. The study population also includes participants who are receiving Yescarta for relapsed or refractory large B-cell lymphoma or follicular lymphoma.
Intervention: Yescarta
Outcomes
Primary Outcomes
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
Time Frame: up to Day 14 of Parts 1 and 2
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).
Secondary Outcomes
- Duration of All Grades of CRS Occurring by Day 28 After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading(up to Day 56 of Parts 1 and 2)
- Duration of ICANS Occurring by Day 28 After IEC Therapy Using the ICANS Consensus Grading, Regardless of CRS(up to Day 28 of Parts 1 and 2)
- Time to Onset of All Grades of CRS by Day 28 After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading(up to Day 28 of Parts 1 and 2)
- Percentage of Participants With ≥Grade 2 CRS by Day 28 After First IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading(up to Day 28 of Parts 1 and 2)
- Time to Onset of ICANS Using the ICANS Consensus Grading, Regardless of CRS, by Day 28 After IEC Therapy(up to Day 28 of Parts 1 and 2)
- Percentage of Participants With Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) by Day 28 After IEC Therapy, Assessed by Using the ICANS Consensus Grading(up to Day 28 of Parts 1 and 2)
- Percentage of Participants With Any ≥Grade 3 Cytopenias Ongoing at Day 28(Day 28 of Parts 1 and 2)
- Percentage of Participants With Any Grade of CRS at 48 Hours After IEC Therapy, Assessed by Using ASBMT CRS Consensus Grading(up to Day 2 of Parts 1 and 2)
- Percentage of Participants Requiring More Than 1 Dose of Dexamethasone (or Equivalent) for ICANS(up to Day 30 of Parts 1 and 2)
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Except CRS and ICANS(from at Day -3 through the duration of safety follow-up (up to Day 56) for Parts 1 and 2)
- Percentage of Participants Who Were Treated With Tocilizumab for CRS(up to Day 56 of Parts 1 and 2)