Diffuse Large B Cell LymphomaPhase 2NCT05757219
Itacitinib Pre-modulation in DLBCL Receiving CAR T Cell Therapy
A Phase 2 study testing Itacitinib and Chimeric antigen receptor (CAR) T-cell therapy in people with Diffuse Large B Cell Lymphoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma
- What is being tested?
- Itacitinib and Chimeric antigen receptor (CAR) T-cell therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 19 May 2023to Feb 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33617
Kelsey Lee, 813-745-8228, ICETtrials@moffitt.org
Michael Jain, MD, PhD
About this study
Official title: A Phase 2, Single-Arm, Open-Label Study Using Itacitinib as Pre-Modulation in Patients With Diffuse Large B-Cell Lymphoma (DLBCL) Receiving CAR-T-Cell Therapy
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).
Read the detailed description
This is a phase 2, single-arm, open-label study to assess the safety and efficacy of once daily itacitinib oral administration in patients with diffuse large B-Cell lymphoma (DLBCL) who will receive CAR-T-cell therapy with axicabtagene ciloleucel (Axi-cel) and have been found to have high levels of systemic inflammation. Approximately n=27 adult males and females, 18 years or older, who will receive treatment for diffuse large B-cell lymphoma (DLBCL) at the Moffitt Cancer Center with a ferritin level greater than 400 ng/ml and C-reactive protein (CRP) level greater than 2 mg/dl (20 mg/l) at screening will be enrolled. Study regimen will consist of 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). The exact number of days between apheresis and CAR T cell infusion may vary based on CAR T cell manufacturing turnaround. A single infusion of axi-cel therapy will be administered on Day 0. Investigators hypothesize that pre-modulation with itacitinib started approximately 4 weeks prior to CAR-T-cell therapy with axi-cel will improve patient outcomes in those patients with diffuse large B-cell lymphoma (DLBCL) who express high levels of systemic inflammation.
- Conditions
- Diffuse Large B Cell Lymphoma
- Being tested
- Itacitinib, Chimeric antigen receptor (CAR) T-cell therapy
- Keywords
- CAR-T, chimeric antigen receptor (CAR) T-cell therapy
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ItacitinibDrug
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 therapyBiological
Also called YESCARTA, Axi-cel
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.
| Study group | Role | What they receive |
|---|---|---|
| Pre-Modulation Treatment | Experimental | 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) Receives: Drug: Itacitinib; Biological: Chimeric antigen receptor (CAR) T-cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Progression Free Survival is defined as the time from start of treatment to the time of disease progression or death. Among patients treated with axi-cel who have a ferritin >400 ng/ml and CRP>2 mg/dl at the time of apheresis, the 6 month PFS was 25%. The primary endpoint of this study will be met if pre-modulation with itacitinib followed by axi-cel leads to a 6 month PFS of 45% or higher.
Measured: at 6 months
Secondary outcomes (5)
Incidence of Severe Cytokine Release Syndrome (CRS)
Number of participants who experience severe (grade 3 or higher by ASTCT criteria) CRS in the first 30 days after CAR-T infusion.
Measured: Up to 3 months
Incidence of Severe Immune efflector cell Associated Neurotoxicity Syndrome (ICANS)
Number of participants who experience severe (grade 3 or higher by ASTCT criteria) ICANS in the first 30 days after CAR-T infusion per CTCAE 5.0.
Measured: Up to 3 months
Overall Response Rate
Overall Response Rate is defined as the rate of the best overall response as complete response (CR) or partial response (PR) by Lugano Response Criteria. Lugano Criteria are based on PET or bidimensional tumor measurements on computerized tomography (CT).
Measured: at 6 months
Overall Survival (OS)
Overall Survival (OS) will be measured from the initial date of treatment to the recorded date of death.
Measured: up to 27months
Progression Free Survival (PFS)
Progression Free Survival is defined as the time from start of treatment to the time of disease progression or death. Among patients treated with axi-cel who have a ferritin >400 ng/ml and CRP>2 mg/dl at the time of apheresis, the 6 month PFS was 25%. The primary endpoint of this study will be met if pre-modulation with itacitinib followed by axi-cel leads to a 6 month PFS of 45% or higher.
Measured: up to 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2023
- Study start19 May 2023
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor
- Investigators
- Michael Jain, MD, PhD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05757219
- Sponsor's protocol ID
- MCC-21892
- Status last verified
- Sep 2026
- First submitted
- 24 Feb 2023
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Single-Arm, Open-Label Study Using Itacitinib as Pre-Modulation in Patients With Diffuse Large B-Cell Lymphoma (DLBCL) Receiving CAR-T-Cell Therapy
- ClinicalTrials.gov ID
- NCT05757219
- Acronym / sponsor ID
- MCC-21892
- Conditions
- Diffuse Large B Cell Lymphoma
- Keywords
- CAR-T, chimeric antigen receptor (CAR) T-cell therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Incyte Corporation
- Study start
- 19 May 2023 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 7 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a phase 2, single-arm, open-label study to assess the safety and efficacy of once daily itacitinib oral administration in patients with diffuse large B-Cell lymphoma (DLBCL) who will receive CAR-T-cell therapy with axicabtagene ciloleucel (Axi-cel) and have been found to have high levels of systemic inflammation. Approximately n=27 adult males and females, 18 years or older, who will receive treatment for diffuse large B-cell lymphoma (DLBCL) at the Moffitt Cancer Center with a ferritin level greater than 400 ng/ml and C-reactive protein (CRP) level greater than 2 mg/dl (20 mg/l) at screening will be enrolled. Study regimen will consist of 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). The exact number of days between apheresis and CAR T cell infusion may vary based on CAR T cell manufacturing turnaround. A single infusion of axi-cel therapy will be administered on Day 0. Investigators hypothesize that pre-modulation with itacitinib started approximately 4 weeks prior to CAR-T-cell therapy with axi-cel will improve patient outcomes in those patients with diffuse large B-cell lymphoma (DLBCL) who express high levels of systemic inflammation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pre-Modulation Treatment | Experimental | Drug: Itacitinib, Biological: Chimeric antigen receptor (CAR) T-cell therapyParticipants 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
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 |
|---|---|---|
| ItacitinibParticipants 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. | Drug | Pre-Modulation Treatment |
| Chimeric antigen receptor (CAR) T-cell therapyAlso: YESCARTA, Axi-celYescarta 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. | Biological | Pre-Modulation Treatment |
Primary outcome
Progression Free Survival (PFS)
Time frame: at 6 months
Progression Free Survival is defined as the time from start of treatment to the time of disease progression or death. Among patients treated with axi-cel who have a ferritin >400 ng/ml and CRP>2 mg/dl at the time of apheresis, the 6 month PFS was 25%. The primary endpoint of this study will be met if pre-modulation with itacitinib followed by axi-cel leads to a 6 month PFS of 45% or higher.
5 secondary outcomes
Incidence of Severe Cytokine Release Syndrome (CRS)
Time frame: Up to 3 months
Incidence of Severe Immune efflector cell Associated Neurotoxicity Syndrome (ICANS)
Time frame: Up to 3 months
Overall Response Rate
Time frame: at 6 months
Overall Survival (OS)
Time frame: up to 27months
Progression Free Survival (PFS)
Time frame: up to 27 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Michael Jain, MD, PhD principal investigator
Moffitt Cancer Center
1 site 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 and Chimeric antigen receptor (CAR) T-cell therapy in people with Diffuse Large B Cell Lymphoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site 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 9 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2026.