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

• ClinicalTrials.gov Identifier: NCT04071366
• Recruitment Status: Recruiting
• First Posted: August 28, 2019
• Last Update Posted: October 26, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: August 26, 2019
• First Posted Date: August 28, 2019
• Last Update Posted Date: October 26, 2022
• Actual Study Start Date: February 7, 2020
• Estimated Primary Completion Date: June 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2019)

Proportion of participants who develop ≥ Grade 2 CRS [ Time Frame: Day 14 ]

Assessed using American Society for Blood and Marrow Transplantation (ASBMT) CRS Consensus Grading.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 17, 2022)

• Proportion of participants with immune effector cell-associated neurotoxicity syndrome (ICANS) after IEC therapy [ Time Frame: Day 28 ]
  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.
• Duration of ICANS regardless of CRS [ Time Frame: Day 28 ]
  Assessed using the ICANS Consensus Grading.
• Duration of all grades of CRS [ Time Frame: Day 28 ]
  Assessed using ASBMT CRS Consensus Grading.
• Proportion of participants with any grade of CRS after IEC therapy [ Time Frame: 48 hours ]
  Assessed using ASBMT CRS Consensus Grading.
• Proportion of participants with ≥ Grade 2 CRS after first IEC therapy [ Time Frame: Day 28 ]
  Assessed using ASBMT CRS Consensus Grading.
• Number of treatment-emergent adverse events [ Time Frame: Day -3 through safety follow-up, up to approximately 60 days. ]
  Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of itacitinib.
• Number of Particpants with ≥ Grade 3 Cytopenias [ Time Frame: Through end of study, up to 90 days. ]
  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.
• Number of hospital admissions for participants with CRS and/or ICANS [ Time Frame: Through end of study, up to 180 days. ]
  Assessed using ASBMT CRS Consensus Grading.
• Duration of hospital stay for participants with CRS and/or ICANS [ Time Frame: Through end of study, up to 180 days. ]
  Assessed using ASBMT CRS Consensus Grading.
• Percentage of participants who were treated with tocilizumab for CRS [ Time Frame: 30 days ]
  Assessed using ASBMT CRS Consensus Grading.
• Percentage of participants requiring >1 dose of dexamethasone (or equivalent) for ICANS. [ Time Frame: 30 days ]
  Assessed using the ICANS Consensus Grading.

Original Secondary Outcome Measures (submitted: August 26, 2019)

• Proportion of participants with immune effector cell-associated neurotoxicity syndrome (ICANS) after IEC therapy [ Time Frame: Day 28 ]
  Assessed using the ICANS Consensus Grading.
• Duration of ICANS regardless of CRS [ Time Frame: Day 28 ]
  Assessed using the ICANS Consensus Grading.
• Duration of all grades of CRS [ Time Frame: Day 28 ]
  Assessed using ASBMT CRS Consensus Grading.
• Proportion of participants with any grade of CRS after IEC therapy [ Time Frame: 48 hours ]
  Assessed using ASBMT CRS Consensus Grading.
• Proportion of participants with ≥ Grade 2 CRS after first IEC therapy [ Time Frame: Day 28 ]
  Assessed using ASBMT CRS Consensus Grading.
• Number of treatment-emergent adverse events [ Time Frame: Day -3 through safety follow-up, up to approximately 60 days. ]
  Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of itacitinib.
• Number of hospital admissions for participants with CRS and/or ICANS [ Time Frame: Through end of study, up to 180 days. ]
• Duration of hospital stay for participants with CRS and/or ICANS [ Time Frame: Through end of study, up to 180 days. ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Part 1: Singe Group Assignment Part 2: Parallel Assignment

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Part 1 is not masked (open label). Part 2 is double blinded (participant, investigator)

Primary Purpose: Prevention

• Condition: Cytokine Release Syndrome

Intervention

• Drug: Itacitinib
  Part 1: Itacitinib 200 mg once daily for 30 days. Part 2: Itacitinib 200 mg twice daily for 30 days.
  Other Name: INCB039110
• Drug: 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.
  Other Name: CAR-T cell therapy
• Drug: 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.
  Other Name: axicabtagene ciloleucel KTE-C19

Study Arms

• Experimental: 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.
  Interventions:

  • Drug: Itacitinib
  • Drug: Immune effector cell therapy
• Experimental: 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.
  Interventions:

  • Drug: Itacitinib
  • Drug: Placebo
  • Biological: Yescarta

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 8, 2022): 108
• Original Estimated Enrollment (submitted: August 26, 2019): 62
• Estimated Study Completion Date: November 15, 2023
• Estimated Primary Completion Date: June 15, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Incyte Corporation Call Center (US); 1.855.463.3463; medinfo@incyte.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04071366
• Other Study ID Numbers: INCB 39110-211
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Peter Langmuir, MD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: October 2022