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).
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 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.
Single group
Itacitinib
DrugParticipants 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
Biological/VaccineYescarta 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.
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.
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.
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.
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).
Overall Survival (OS)
Overall Survival (OS) will be measured from the initial date of treatment to the recorded date of death.
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H. Lee Moffitt Cancer Center and Research Institute
Lead sponsor
Incyte Corporation
Collaborator
