Phase 2 Pilot Study to Evaluate Efficacy and Safety of Anakinra to Prevent CD19-Targeted CAR-T Cell-Related Cytokine Release Syndrome (CRS) and Neurotoxicity in Patients With B Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Absence of Any Grade Cytokine Release Syndrome (CRS)
研究概览
简要总结
This phase II trial studies how well anakinra works in decreasing the occurrence of cytokine release syndrome (CRS) and damage to the nerves (neurotoxicity) in patients with B-cell non-Hodgkin lymphoma who are receiving CD-19 targeted chimeric antigen receptor T-cell (CAR-T) therapy. CAR-T cell therapy may be complicated by two potentially life-threatening side effects: CRS and neurotoxicity. Anakinra is a drug typically used to treat rheumatoid arthritis, but may also help in preventing CAR-T cell-related cytokine release syndrome and neurotoxicity.
详细描述
OUTLINE:
Patients receive anakinra intravenously (IV) [previously subcutaneously (SC) for some patients] over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, positron emission tomography/computed tomography (PET/CT) or CT, bone marrow aspirate (BMA) and biopsy (if clinically indicated), and lumbar puncture (if clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
After completion of lisocabtagene maraleucel infusion, patients are followed up periodically for up to 90 days.
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
- •Subjects must be 18 years of age or older
- •Karnofsky performance status of >= 60%
- •Patients with B-cell non-Hodgkin lymphoma (B-NHL) and eligible for treatment with liso-cel. Patients treated with non-conforming (out-of-specification) liso-cell may remain on study.
- •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 subjects must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last dose of anakinra
- •Ability to understand and provide informed consent
排除标准
- •Subjects requiring ongoing daily corticosteroid therapy at a dose of > 15 mg of prednisone per day (or equivalent). Pulsed corticosteroid use for disease control is acceptable
- •Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the principal investigator (PI)
- •Known hypersensitivity to Escherichia € coli-derived proteins, anakinra, or to any component of the product
- •Major organ dysfunction defined as:
- •Serum creatinine > 2.5 mg/dL
- •Significant hepatic dysfunction (Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 5x upper limit of normal; bilirubin > 3.0 mg/dL) unless due to malignancy or Gilbert's syndrome in the opinion of the PI or designee
- •Subjects with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing. Those with a forced expiratory volume in 1 second (FEV1) of < 50% of predicted or diffusion capacity of the lung 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
研究组 & 干预措施
Prevention (anakinra, lisocabtagene maraleucel)
Patients receive anakinra IV (previously SC) over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
干预措施: Anakinra (Biological)
Prevention (anakinra, lisocabtagene maraleucel)
Patients receive anakinra IV (previously SC) over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
干预措施: X-Ray Imaging (Procedure)
Prevention (anakinra, lisocabtagene maraleucel)
Patients receive anakinra IV (previously SC) over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
干预措施: Positron Emission Tomography (Procedure)
Prevention (anakinra, lisocabtagene maraleucel)
Patients receive anakinra IV (previously SC) over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
干预措施: Computed Tomography (Procedure)
Prevention (anakinra, lisocabtagene maraleucel)
Patients receive anakinra IV (previously SC) over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
干预措施: Bone Marrow Aspiration (Procedure)
Prevention (anakinra, lisocabtagene maraleucel)
Patients receive anakinra IV (previously SC) over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
干预措施: Bone Marrow Biopsy (Procedure)
Prevention (anakinra, lisocabtagene maraleucel)
Patients receive anakinra IV (previously SC) over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
干预措施: Lumbar Puncture (Procedure)
Prevention (anakinra, lisocabtagene maraleucel)
Patients receive anakinra IV (previously SC) over 10-30 minutes daily on days 0-13 and lisocabtagene maraleucel via infusion on day 0. Patients should also undergo at screening an x-ray, PET/CT or CT, BMA and biopsy (as clinically indicated), and lumbar puncture (as clinically indicated), and at follow-up as clinically indicated. Patients also undergo blood sample collection on study.
干预措施: Biospecimen Collection (Procedure)
结局指标
主要结局
Absence of Any Grade Cytokine Release Syndrome (CRS)
时间窗: Up to 28 days after lisocabtagene maraleucel (liso-cel) infusion
Will assess the efficacy of anakinra in preventing the occurrence of any grade CRS using the Bayesian optimal phase 2 design. Assessed based on the ASTCT Consensus Grading for CRS and Neurotoxicity Associated with Immune Effector Cell.
次要结局
- CRS Grade(Up to 28 days after liso-cel infusion)
- Disease Response to Liso-cel(Approximately 90 days after liso-cel infusion)
- ICANS Grade(Up to 28 days after liso-cel infusion)
- Rate of Hospitalization After Liso-cel Treatment(Up to 28 days after liso-cel infusion)
- Duration of Hospitalization After Liso-cel Treatment(Up to 28 days after liso-cel infusion)
- Corticosteroid Usage After Liso-cel Treatment(Up to 28 days after liso-cel infusion)
- Adverse Events (AEs)(Up to 28 days after liso-cel infusion)
研究者
Jordan Gauthier
Associate Professor
Fred Hutchinson Cancer Center