This phase I/II trial tests the safety and how well intravenous interferon-beta-1a (FP-1201) works in preventing toxicities after CD19-directed chimeric antigen receptor (CAR) T-cell therapy in patients with B-cell cancers that has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Interferon beta-1a is in a class of medications called immunomodulators. It works by protecting the lining of blood vessels, and preventing brain inflammation. Giving FP-1201 may prevent cytokine release syndrome (CRS) and immune effector cell associated-neurotoxicity syndrome (ICANS) toxicities in patients receiving CD19 CAR T-cell therapy with recurrent or refractory B-cell malignancies.
OUTLINE: This is a dose-escalation study of FP-1201. Patients undergo leukapheresis prior to treatment and receive FP-1201 intravenously (IV) for 3 days every 24 hours from day -3 through day -1 or for 5 days every 24 hours from day -5 through day -1 or on day -5, day -3, and day -1. Patients may receive lymphodepletion chemotherapy with either cyclophosphamide IV and fludarabine IV on days -5, -4, -3 followed by axi-cel IV or brexu-cel IV on day 0 or fludarabine IV over 30 minutes on days -4, -3, and -2 and cyclophosphamide IV over 60 minutes on day -2 followed by brexu-cel IV on day 0. Patients undergo x-ray imaging and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT as well as lumbar puncture (LP) for cerebral spinal fluid (CSF) collection and/or bone marrow aspiration and biopsy as clinically indicated during screening and follow-up. Patients undergo blood sample collection on study and during follow-up as well as a tissue biopsy during screening and follow-up. After completion of study treatment, patients are followed up to 28 days and 90 days, then long-term for up to 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Given IV
Undergo x-ray
Undergo ECHO
Undergo MUGA
Undergo CT
Undergo PET/CT
Undergo LP
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo blood and CSF sample collection
Undergo tissue biopsy
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Dose-limiting toxicity (DLT) rates
Will be summarized in the DLT evaluable population. Final DLT rates at each dose level will be estimated by isotonic regression by applying the pooled adjacent violators algorithm. The target toxicity rate is 30%.
Time frame: Within 14 days after the last administration of interferon-beta-1a (FP-1201)
Incidence of adverse events (AEs)
Type, frequency, and severity of AEs according to the National Cancer Institutes Common Terminology Criteria for Adverse Events version 5.0.
Time frame: From the first dose of FP-1201 through day 28 after chimeric antigen receptor (CAR) T-cell infusion
Cytokine release syndrome (CRS) rates
Will be assessed by any grade and grade \>= 3 by American Society for Transplantation and Cellular Therapy (ASTCT) criteria and will be summarized along the two-sided 95% Clopper-Pearson confidence interval (CI) based on the CRS and ICANS analysis set.
Time frame: From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last
Immune effector cell associated-neurotoxicity syndrome (ICANS) rates
Will be assessed by any grade and grade \>= 3 by ASTCT criteria and will be summarized along the two-sided 95% Clopper-Pearson CI based on the CRS and ICANS analysis set.
Time frame: From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last
Cumulative corticosteroids dose
Will be summarized using descriptive statistics (median, quantiles) based on the CRS and ICANS analysis set.
Time frame: Within 28 days after CAR T-cell infusion
Overall response rate
Will be assessed by the Lugano criteria for B-non-Hodgkin lymphoma (NHL) participants and National Comprehensive Cancer Network (NCCN) criteria for B- acute lymphoblastic leukemia (ALL) participants Will be summarized along with the two-sided Clopper-Pearson CI based on the anti-tumor response evaluable analysis set.
Time frame: 28 days after CAR T-cell infusion
Complete response rate
Will be assessed by the Lugano criteria for B-NHL participants and NCCN criteria for B-ALL participants Will be summarized along with the two-sided Clopper-Pearson CI based on the anti-tumor response evaluable analysis set.
Time frame: 28 days after CAR T-cell infusion
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