Itacitinib Pre-modulation in DLBCL Receiving CAR T Cell Therapy

NCT05757219 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-21892
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  at 6 months

Secondary Outcomes (5)

• Incidence of Severe Cytokine Release Syndrome (CRS)

  Up to 3 months

• Incidence of Severe Immune efflector cell Associated Neurotoxicity Syndrome (ICANS)

  Up to 3 months

• Overall Response Rate

  at 6 months

• Overall Survival (OS)

  up to 27months

• Progression Free Survival (PFS)

  up to 27 months

Study Arms (1)

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)

Drug: Itacitinib; Biological: Chimeric antigen receptor (CAR) T-cell therapy

Interventions

Itacitinib DRUG

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.

Pre-Modulation Treatment

Chimeric antigen receptor (CAR) T-cell therapy BIOLOGICAL

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.

Also known as: YESCARTA, Axi-cel

Pre-Modulation Treatment

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Incyte Corporation: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33617, United States

RECRUITING

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

itacitinib; Receptors, Chimeric Antigen; Automobiles; axicabtagene ciloleucel

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Receptors, Artificial; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Antigen, T-Cell; Receptors, Antigen; Receptors, Immunologic; Receptors, Cytoplasmic and Nuclear; Motor Vehicles; Transportation; Technology, Industry, and Agriculture

Study Officials

• Michael Jain, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: March 7, 2023
• Study Start: May 19, 2023
• Primary Completion (Estimated): June 20, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)