Cytokine Release SyndromePhase 2NCT04071366

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

A Phase 2 study testing Itacitinib, Immune effector cell therapy and Yescarta in people with Cytokine Release Syndrome, run by Incyte Corporation at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Cytokine Release Syndrome
What is being tested?: Itacitinib, Immune effector cell therapy and Yescarta
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 112 participants
Where: 10 sitesUnited States
Study dates: 7 Feb 2020to 22 Aug 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Show all 11Show fewer

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.

Trial locations and contacts

10 sites in 1 country.

City, postcode or hospital

10 sites in 1 country

United States10 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio, 45229
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Washington University School of Medicine
St Louis, Missouri, 63110
Moffitt Cancer Center
Tampa, Florida, 33612

Other trials in United States

About this study

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

Conditions: Cytokine Release Syndrome
Being tested: Itacitinib, Immune effector cell therapy, Placebo, Yescarta
Keywords: Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, Janus kinase inhibitor, immune effector cell therapy
Medical subject headings: Cytokine Release Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ItacitinibDrug
Also called INCB039110
Part 1: Itacitinib 200 mg once daily for 30 days. Part 2: Itacitinib 200 mg twice daily for 30 days.
Immune effector cell therapyDrug
Also called CAR-T 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.
PlaceboDrug
Participants will receive placebo twice daily.
YescartaBiological
Also called axicabtagene ciloleucel KTE-C19
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.

Study groups in NCT04071366
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Itacitinib; Drug: Placebo; Biological: Yescarta

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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
Participants were monitored for signs and symptoms of ICANS, if symptoms developed at any point after IEC. ICANS Consensus Grading Criteria were used to assess 5 domains of neurotoxicity: orientation (orient to year, month, city, and hospital), naming (naming 3 objects), following commands (follow commands such as: show me 2 fingers or close your eyes and stick out your tongue), writing (ability to write a standard sentence), and attention (count backwards from 100 by 10). Each domain is associated with a certain number of points, which are summed to generate a total score. Score 10: no impairment; score 7-9: Grade 1 ICANS; score 3-6: Grade 2 ICANS; score 0-2: Grade 3 ICANS.
Measured: 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
Participants were monitored for signs and symptoms of ICANS, if symptoms developed at any point after IEC. ICANS Consensus Grading Criteria were used to assess 5 domains of neurotoxicity: orientation (orient to year, month, city, and hospital), naming (naming 3 objects), following commands (follow commands such as: show me 2 fingers or close your eyes and stick out your tongue), writing (ability to write a standard sentence), and attention (count backwards from 100 by 10). Each domain is associated with a certain number of points, which are summed to generate a total score. Score 10: no impairment; score 7-9: Grade 1 ICANS; score 3-6: Grade 2 ICANS; score 0-2: Grade 3 ICANS.
Measured: 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
Participants were monitored for signs and symptoms of ICANS, if symptoms developed at any point after IEC. ICANS Consensus Grading Criteria were used to assess 5 domains of neurotoxicity: orientation (orient to year, month, city, and hospital), naming (naming 3 objects), following commands (follow commands such as: show me 2 fingers or close your eyes and stick out your tongue), writing (ability to write a standard sentence), and attention (count backwards from 100 by 10). Each domain is associated with a certain number of points, which are summed to generate a total score. Score 10: no impairment; score 7-9: Grade 1 ICANS; score 3-6: Grade 2 ICANS; score 0-2: Grade 3 ICANS. Duration of ICANS occurring by Day 28 corresponds to the sum of days with non-zero grade ICANS by Day 28.
Measured: 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
The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 1: fever; either no hypotention and/or no hypoxia. Grade 2 CRS: 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 vasopressinc, 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., CPAP, BiPAP, intubation, mechanical ventilation).
Measured: 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
The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 1: fever; either no hypotention and/or no hypoxia. Grade 2 CRS: 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 vasopressinc, 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., CPAP, BiPAP, intubation, mechanical ventilation).
Measured: up to Day 56 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
The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 1: fever; either no hypotention and/or no hypoxia. Grade 2 CRS: 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 vasopressinc, 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., CPAP, BiPAP, intubation, mechanical ventilation).
Measured: up to Day 2 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
The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 1: fever; either no hypotention and/or no hypoxia. Grade 2 CRS: 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 vasopressinc, 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., CPAP, BiPAP, intubation, mechanical ventilation).
Measured: up to Day 28 of Parts 1 and 2
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Except CRS and ICANS
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. For purposes of analysis, all AEs were considered TEAEs unless the AE could unequivocally be defined as not treatment emergent.
Measured: from at Day -3 through the duration of safety follow-up (up to Day 56) for Parts 1 and 2
Percentage of Participants With Any ≥Grade 3 Cytopenias Ongoing at Day 28
Cytopenia is characterized by low levels of white blood cells, red blood cells, or platelets. Analysis used laboratory counts at Day 28.
Measured: Day 28 of Parts 1 and 2
Percentage of Participants Who Were Treated With Tocilizumab for CRS
Tocilizumab and/or corticosteroids for CRS Grade 1 was not allowed per the protocol. However, tocilizumab may have been given as rescue medication for CRS Grade 1 if no improvement was observed within 72 hours from onset, and the participant's medical condition required intervention per investigator judgment.
Measured: up to Day 56 of Parts 1 and 2
Percentage of Participants Requiring More Than 1 Dose of Dexamethasone (or Equivalent) for ICANS
Dexamethasone use as rescue medication for ICANS was assessed.
Measured: up to Day 30 of Parts 1 and 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Feb 202022 Aug 2023

First posted28 Aug 2019
Study start7 Feb 2020
Primary completion23 Feb 2023
Study completion22 Aug 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Cytokine Release SyndromeStudies of the same condition, open and under way.
More trials run by Incyte CorporationThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Model description: Part 1: Singe Group Assignment Part 2: Parallel Assignment
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 112 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04071366
Sponsor's protocol ID: INCB 39110-211
Status last verified: Feb 2024
First submitted: 26 Aug 2019
Last updated: 26 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 40090005
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.
PubMed 32998963

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Cytokine Release Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2 Study of Itacitinib, for the Prevention of Cytokine Release Syndrome Induced by Immune Effector Cell Therapy
ClinicalTrials.gov ID: NCT04071366
Acronym / sponsor ID: INCB 39110-211
Conditions: Cytokine Release Syndrome
Keywords: Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, Janus kinase inhibitor, immune effector cell therapy
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 112 participants (actual)
Lead sponsor: Incyte CorporationIndustry (pharma, biotech, devices)
Study start: 7 Feb 2020 (actual)
Primary completion: 23 Feb 2023 (actual)
Study completion: 22 Aug 2023 (actual)
First posted: 28 Aug 2019 (actual)
Results: Posted 26 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2
Model description: Part 1: Singe Group Assignment Part 2: Parallel Assignment

Arm	Type	Receives
Part 1: Open Label Itacitinib Once Daily	Experimental	Drug: Itacitinib, Drug: Immune effector cell therapyDuring 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.
Part 2: Double-Blind Itacitinib Twice Daily	Experimental	Drug: Itacitinib, Drug: Placebo, Biological: YescartaDuring 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.

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (11 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ItacitinibAlso: INCB039110Part 1: Itacitinib 200 mg once daily for 30 days. Part 2: Itacitinib 200 mg twice daily for 30 days.	Drug	Part 1: Open Label Itacitinib Once Daily, Part 2: Double-Blind Itacitinib Twice Daily
Immune effector cell therapyAlso: CAR-T cell therapyParticipants 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.	Drug	Part 1: Open Label Itacitinib Once Daily
PlaceboParticipants will receive placebo twice daily.	Drug	Part 2: Double-Blind Itacitinib Twice Daily
YescartaAlso: axicabtagene ciloleucel KTE-C19Eligible 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.	Biological	Part 2: Double-Blind Itacitinib Twice Daily

Primary outcome

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).

11 secondary outcomes

Percentage of Participants With Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) by Day 28 After IEC Therapy, Assessed by Using the ICANS Consensus Grading
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: up to Day 56 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
Time frame: up to Day 2 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
Time frame: up to Day 28 of Parts 1 and 2
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Except CRS and ICANS
Time frame: from at Day -3 through the duration of safety follow-up (up to Day 56) for Parts 1 and 2
Percentage of Participants With Any ≥Grade 3 Cytopenias Ongoing at Day 28
Time frame: Day 28 of Parts 1 and 2
Percentage of Participants Who Were Treated With Tocilizumab for CRS
Time frame: up to Day 56 of Parts 1 and 2
Percentage of Participants Requiring More Than 1 Dose of Dexamethasone (or Equivalent) for ICANS
Time frame: up to Day 30 of Parts 1 and 2

Results and safety

Results posted to the registry on 26 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Itacitinib 200 Milligrams (mg) QD + Kymriah	16	11
Part 1: Itacitinib 200 mg QD + Tecartus	12	10
Part 1: Itacitinib 200 mg QD + Yescarta	35	22
Part 2: Itacitinib 200 mg BID + Yescarta	0	0
Part 2: Placebo BID + Yescarta	0	0

Primary outcome: 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. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Part 1: Itacitinib 200 Milligrams (mg) QD + Kymriah n = 16	Part 1: Itacitinib 200 mg QD + Tecartus n = 12	Part 1: Itacitinib 200 mg QD + Yescarta n = 35	Part 2: Itacitinib 200 mg BID + Yescarta n = 23	Part 2: Placebo BID + Yescarta n = 23
Value	12.5 (1.6 to 38.3)	41.7 (15.2 to 72.3)	20.0 (8.4 to 36.9)	17.4 (5.0 to 38.8)	56.5 (34.5 to 76.8)

Part 2: Itacitinib 200 mg BID + Yescarta vs Part 2: Placebo BID + Yescarta: Difference in CRS rate: -0.39 (95% CI -0.6463 to -0.1363), p = 0.0030, One-sided Z-test
Part 1: Itacitinib 200 mg QD + Yescarta vs Part 2: Placebo BID + Yescarta: Difference in CRS rate: -0.37 (95% CI -0.6073 to -0.1231)
Part 1: Itacitinib 200 mg QD + Yescarta vs Part 2: Itacitinib 200 mg BID + Yescarta: Difference in CRS rate: 0.03 (95% CI -0.1778 to 0.2299)

Population analysed: Efficacy Evaluable Analysis Set (EAS): all participants who received at least 1 dose of study drug and received IEC therapy. The exact 95% confidence interval (2-sided) was calculated using the Clopper-Pearson method.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: TEAEs collected from Day -3 through the duration of safety follow-up (up to Day 56) for Parts 1 and 2 have been reported. Deaths occurring up to the end of the study (Day 180) or until early study withdrawal have been reported.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Itacitinib 200 Milligrams (mg) QD + Kymriah	2 of 16 (12.5%)	16 of 16 (100%)	4 of 16
Part 1: Itacitinib 200 mg QD + Tecartus	1 of 12 (8.3%)	12 of 12 (100%)	2 of 12
Part 1: Itacitinib 200 mg QD + Yescarta	9 of 35 (25.7%)	35 of 35 (100%)	9 of 35
Part 1: Itacitinib 200 mg + Any IEC	12 of 63 (19%)	63 of 63 (100%)	15 of 63
Part 2: Itacitinib 200 mg BID + Yescarta	3 of 23 (13%)	22 of 23 (95.7%)	2 of 23
Part 2: Placebo BID + Yescarta	6 of 24 (25%)	24 of 24 (100%)	2 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40090005Frigault 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.
Derived from this study: PubMed 32998963Huarte 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.
Individual participant dataSharing planned: No

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Not yet recruitingPhase 1
CLL-1/CD70 Dual-Target CAR-T Cell Therapy for Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML), Relapsed/Refractory Acute Myeloid Leukemia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Peter Langmuir, MD study director

Incyte Corporation

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Itacitinib, Immune effector cell therapy and Yescarta in people with Cytokine Release Syndrome, run by Incyte Corporation at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: up to Day 14 of Parts 1 and 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04071366, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2024.