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Completed

NCT Number: NCT04071366

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

"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.

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Key information

Conditions

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

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Itacitinib

Drug

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

Other names: INCB039110

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.

Other names: CAR-T cell therapy

Placebo

Drug

Participants will receive placebo 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.

Other names: axicabtagene ciloleucel KTE-C19

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

    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

  1. 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

    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.

  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

    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.

  3. 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

    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.

  4. 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

    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).

  5. 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

    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).

  6. 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

    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).

  7. 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

    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).

  8. 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

    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.

  9. Percentage of Participants With Any ≥Grade 3 Cytopenias Ongoing at Day 28

    Time frame: Day 28 of Parts 1 and 2

    Cytopenia is characterized by low levels of white blood cells, red blood cells, or platelets. Analysis used laboratory counts at Day 28.

  10. Percentage of Participants Who Were Treated With Tocilizumab for CRS

    Time frame: up to Day 56 of Parts 1 and 2

    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.

  11. 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

    Dexamethasone use as rescue medication for ICANS was assessed.

Other outcomes

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

    Time frame: up to Day 180 of Parts 1 and 2

    The number of hospital admissions was assessed through study completion.

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

    Time frame: up to Day 180 of Parts 1 and 2

    The duration of hospital stays was assessed through study completion.

Sponsors and collaborators

Lead sponsor

Incyte Corporation

Industry

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Aug 28, 2019
Registry last updated
Mar 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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