Phase 1/2 Study to Evaluate the Safety, Feasibility, and Efficacy of FP-1201 (Intravenous Interferon-Beta-1a) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Incidence of adverse events (AEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be 18 years of age or older
- •Karnofsky performance status of >= 60%
- •Participants eligible for treatment with axi-cel or brexu-cel
- •Negative serum pregnancy test within 2 weeks of enrollment for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
- •Fertile male and female participants must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last dose of FP-1201
- •Ability to understand and provide informed consent
排除标准
- •Known hypersensitivity to natural or recombinant interferon beta, albumin or any other component of the formulation
- •Estimated creatinine clearance (Cockcroft and Gault) =< 60 mL/min
- •Significant proteinuria defined as 2+ or 3+ proteinuria or urinary protein >= 1g/24h
- •Severe hepatic dysfunction defined as group C of the National Cancer Institute Organ Dysfunction Working Group hepatic impairment criteria (total bilirubin > 3x upper limit of normal [ULN] with any aspartate aminotransferase [AST] or alanine transaminase [AL]T value), or AST or ALT > 3x ULN, unless due to malignancy or Gilbert's syndrome in the opinion of the principal investigator (PI) or designee
- •Participants with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing, as clinically indicated. Those with an forced expiratory volume in the first second (FEV1) of < 50 % of predicted or diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected) < 40% will be excluded
- •Significant cardiovascular abnormalities as defined by any one of the following:
- •New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension
- •Uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of < 35%
- •Uncontrolled serious and active infection
- •Corticosteroid use (> 20mg/day of prednisone, or equivalent) within 7 days prior to first FP-1201 administration
结局指标
主要结局
Incidence of adverse events (AEs)
时间窗: From the first dose of FP-1201 through day 28 after chimeric antigen receptor (CAR) T-cell infusion
Type, frequency, and severity of AEs according to the National Cancer Institutes Common Terminology Criteria for Adverse Events version 5.0.
Dose-limiting toxicity (DLT) rates
时间窗: Within 14 days after the last administration of interferon-beta-1a (FP-1201)
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%.
次要结局
- Immune effector cell associated-neurotoxicity syndrome (ICANS) rates(From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last)
- Overall response rate(28 days after CAR T-cell infusion)
- Cytokine release syndrome (CRS) rates(From the time of CAR T-cell infusion through day 28 after CAR T-cell infusion or until resolution, whichever happens last)
- Complete response rate(28 days after CAR T-cell infusion)
- Cumulative corticosteroids dose(Within 28 days after CAR T-cell infusion)