Recruiting
Phase 2

Itacitinib

Sponsor:

H. Lee Moffitt Cancer Center and Research Institute

Code:

NCT05757219

Conditions

Diffuse Large B Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Itacitinib

Chimeric antigen receptor (CAR) T-cell therapy

Study Details

Brief summary:

The purpose of the study is to assess the safety and efficacy of once daily itacitinib oral administration in participants with diffuse large B-cell lymphoma (DLBCL) who will receive CAR-T cell therapy with axicabtagene ciloleucel (axi-cel).

Conditions

Diffuse Large B Cell Lymphoma

Study ID

NCT05757219

Start date

May 19, 2023

Status verified date

Mar, 2026

Completion date

Jan, 2027

Anticipated

Primary completion date

Jun 20, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients with a histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) who plan to receive treatment at the Moffitt Cancer Center/
  • Adult males or females who are 18 years of age or older at time of signing informed consent.
  • Must have ability to comprehend and the willingness to sign written informed consent for study participation.
  • Eligible to receive CAR-T cell therapy (axicabtagene ciloleucel) for DLBCL and histological variants.
  • Patients must have a serum ferritin level above 400 mg/mL and C-reactive protein level above 2 mg/dL (20 mg/L) at screening.
  • ECOG performance status 0 to 2.
  • The effects of Itacitinib on the developing human fetus are unknown. For this reason and because Janus kinase (JAK)1-selective inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation as outlined in criteria below: (a) Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow up and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants in their understanding confirmed.(b) Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose of Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed. (c) Women of non-childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR >= 12 months of amenorrhea) are eligible.
  • Patients must be ineligible for stem cell transplant at screening on the basis of active lymphoma.
  • Patients must meet laboratory parameters at screening as defined in protocol

Exclusion Criteria:

  • Patients who are currently receiving or who have received any investigational study agent ≤4 weeks prior to screening visit are ineligible.
  • Prior treatment with chimeric antigen receptor (CAR) T-cell therapy.
  • Participants with clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from screening, New York Health Association III or IV heart failure, and circulatory collapse requiring vasopressor or inotropic support
  • Participants with arrhythmias that are not stable on a medical management program within 2 weeks of screening are also excluded.
  • Participants with arrhythmias that are not stable on a medical management program within 2 weeks of screening are also excluded.
  • Evidence of active uncontrolled/untreated infection (viral, bacterial, fungal, opportunistic) of any origin.
  • Participants with a known history or prior diagnosis of immunologic or inflammatory/autoimmune disease affecting the CNS, and unrelated to their disease under study or previous treatment.
  • Known positive Human immunodeficiency virus (HIV) status.
  • Participants with evidence of active and/or chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Participants with a history of hepatitis C virus (HCV) infection, HCV must have been treated and cured.
  • Participants who require the concurrent use of chronic systemic steroids or immunosuppressant medications. Steroids should not be given within 5 days prior to leukapheresis. Concomitant bridging steroids (section 6.6) are allowed after leukapheresis.
  • Known hypersensitivity or severe reaction to itacitinib, similar compounds, or excipients or itacitinib.
  • Participants who have not recovered from adverse events (AEs) due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1), with the exception of stable Grade 2 peripheral neuropathy and/or any grade alopecia.
  • Pregnant or nursing (breast-feeding) women are excluded from this study because there is an unknown but potential risk to using itacitinib in pregnant or nursing women.
  • Any condition that would, in the investigator's judgement, interfere with full participation in the study, including administration of itacitinib and attending required study visits (if outpatient); pose a significant risk to the participant; or interfere with interpretation of study data.
  • Inability of the participant to swallow and retain oral medication.
  • Participants receiving any medications or substances that are strong inhibitors of CYP3A4 are ineligible. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.

Study Design

Enrollment

27 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Pre-Modulation Treatment

Participants will receive itacitinib 200 mg PO QD beginning at time of apheresis approximately 4-6 weeks prior to CAR-T-cell therapy and will continue until Day 30 (30 Days Post-CAR-T-cell therapy)

Interventions

Itacitinib

Participants start itacitinib 200 mg PO once daily within 1-4 days after apheresis while awaiting CAR-T-cell manufacturing, which is expected to take approximately from week -4 until day -7. Patients will remain on itacitinib 200 mg PO once daily from initiation until 30 days post-CAR-T-cell therapy (Day 30) including throughout lymphodepleting chemotherapy period (Days -5, -4, -3) and axi-cel infusion (Day 0) for a total of approximately 58 doses.

Chimeric antigen receptor (CAR) T-cell therapy

Yescarta is an autologous anti-CD19 CAR T cell therapy manufactured from the patient's own T cells, which have been extracted and then reprogrammed with CAR molecules to help the T cells recognize cancer cells. The reengineered T cells are infused back into the patient to attack the cancer.

Primary outcome measure

  • Progression Free Survival (PFS) [ Time Frame: at 6 months ]

Central Contacts and Locations

Locations

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33617

Contacts

Kelsey Lee

813-745-8228ICETtrials@moffitt.org

Principal Investigator:

Michael Jain, MD, PhD

More Information

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Last update posted

Mar 31, 2026

Last verified

Mar, 2026

Keywords

  • CAR-T
  • chimeric antigen receptor (CAR) T-cell therapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by H. Lee Moffitt Cancer Center and Research Institute on 2026-03-31.