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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cytokine Release Syndrome

Intervention / Treatment
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* Drug: Itacitinib
* Drug: Immune effector cell therapy
* Drug: Placebo
* Biological: Yescarta


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1: Singe Group Assignment Part 2: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Open Label Itacitinib Once Daily<br>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. | Drug: Itacitinib<br>* Part 1: Itacitinib 200 mg once daily for 30 days. Part 2: Itacitinib 200 mg twice daily for 30 days.<br>* Other names: INCB039110;Drug: Immune effector cell therapy<br>* 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.<br>* Other names: CAR-T cell therapy;|
| Experimental: Part 2: Double-Blind Itacitinib Twice Daily<br>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. | Drug: Itacitinib<br>* Part 1: Itacitinib 200 mg once daily for 30 days. Part 2: Itacitinib 200 mg twice daily for 30 days.<br>* Other names: INCB039110;Drug: Placebo<br>* Participants will receive placebo twice daily.<br>Biological: Yescarta<br>* 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.<br>* Other names: axicabtagene ciloleucel KTE-C19;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who develop ≥ Grade 2 CRS | Assessed using American Society for Blood and Marrow Transplantation (ASBMT) CRS Consensus Grading. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with immune effector cell-associated neurotoxicity syndrome (ICANS) after IEC therapy | Assessed using the ICANS Consensus Grading. Complete response or partial response for ICANS is defined as either complete disappearance or decrease in the grade of severity as measured by ASTCT Consensus Grading for ICANS. The ASTCT grade is from 1 to 5 for ICANS with 1 being mild symptoms and 5 being severe symptoms. | Day 28 | 
| Duration of ICANS regardless of CRS | Assessed using the ICANS Consensus Grading. | Day 28 | 
| Duration of all grades of CRS | Assessed using ASBMT CRS Consensus Grading. | Day 28 | 
| Proportion of participants with any grade of CRS after IEC therapy | Assessed using ASBMT CRS Consensus Grading. | 48 hours | 
| Proportion of participants with ≥ Grade 2 CRS after first IEC therapy | Assessed using ASBMT CRS Consensus Grading. | Day 28 | 
| Number of treatment-emergent adverse events | Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of itacitinib. | Day -3 through safety follow-up, up to approximately 60 days. | 
| Number of Particpants with ≥ Grade 3 Cytopenias | Cytopenia is diagnosed with a blood test called a complete blood count (CBC). A CBC shows white blood cell, red blood cell, and platelet counts. | Through end of study, up to 90 days. | 
| Number of hospital admissions for participants with CRS and/or ICANS | Assessed using ASBMT CRS Consensus Grading. | Through end of study, up to 180 days. | 
| Duration of hospital stay for participants with CRS and/or ICANS | Assessed using ASBMT CRS Consensus Grading. | Through end of study, up to 180 days. | 
| Percentage of participants who were treated with tocilizumab for CRS | Assessed using ASBMT CRS Consensus Grading. | 30 days | 
| Percentage of participants requiring >1 dose of dexamethasone (or equivalent) for ICANS. | Assessed using the ICANS Consensus Grading. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, Janus kinase inhibitor, immune effector cell therapy