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

NCT04071366 | Completed Phase 2 Results FDA Drug

• 1 other identifier: INCB 39110-211
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 10

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.

Conditions

Cytokine Release Syndrome

Keywords

Cytokine release syndrome; immune effector cell-associated neurotoxicity syndrome; Janus kinase inhibitor; immune effector cell therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• 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

• 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

• 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

• 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

Other Outcomes (2)

• Number of Hospital Admissions for Participants With CRS and/or ICANS by the End of the Study

  up to Day 180 of Parts 1 and 2

• Duration of Hospital Stay for Participants With CRS and/or ICANS by End of Study

  up to Day 180 of Parts 1 and 2

Study Arms (2)

Part 1: Open Label Itacitinib Once Daily

EXPERIMENTAL

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; Drug: Immune effector cell therapy

Part 2: Double-Blind Itacitinib Twice Daily

EXPERIMENTAL

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; Drug: Placebo; Biological: Yescarta

Interventions

Itacitinib DRUG

Part 1: Itacitinib 200 mg once daily for 30 days. Part 2: Itacitinib 200 mg twice daily for 30 days.

Also known as: INCB039110

Part 1: Open Label Itacitinib Once Daily; Part 2: Double-Blind Itacitinib Twice Daily

Immune effector cell therapy DRUG

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.

Also known as: CAR-T cell therapy

Part 1: Open Label Itacitinib Once Daily

Placebo DRUG

Participants will receive placebo twice daily.

Part 2: Double-Blind Itacitinib Twice Daily

Yescarta BIOLOGICAL

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.

Also known as: axicabtagene ciloleucel KTE-C19

Part 2: Double-Blind Itacitinib Twice Daily

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (10)

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• Frigault MJ, Maziarz RT, Park JH, Lazaryan A, Shah NN, Svoboda J, Lekakis L, Reshef R, Phillips CL, Burke L, Lei J, Pratta M, Morariu-Zamfir R, DiPersio JF. Itacitinib for the prevention of IEC therapy-associated CRS: results from the 2-part phase 2 INCB 39110-211 study. Blood. 2025 Jul 24;146(4):422-436. doi: 10.1182/blood.2024026586.

  PMID: 40090005 DERIVED

• 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.

  PMID: 32998963 DERIVED

MeSH Terms

Conditions

Cytokine Release Syndrome

Interventions

itacitinib; INCB039110; Immunotherapy, Adoptive; axicabtagene ciloleucel

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Peter Langmuir, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Part 1 is not masked (open label). Part 2 is double blinded (participant, investigator)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1: Singe Group Assignment Part 2: Parallel Assignment

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: August 28, 2019
• Study Start: February 7, 2020
• Primary Completion: February 23, 2023
• Study Completion: August 22, 2023
• Last Updated: March 26, 2024
• Results First Posted: March 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)