A Phase II Pilot Study to Evaluate the Role of Siltuximab in Treatment of Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) Related to Chimeric Antigen Receptor T-Cell Therapy (CAR-T) in Hematological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Participants with a complete response for cytokine release syndrome (CRS)
研究概览
简要总结
This study will evaluate the use of siltuximab to decrease the severity of cytokine release syndrome (CRS) and immune effector cell-associated neurological syndrome (ICANS) in patients who will receive chimeric antigen receptor (CAR) T-cell therapy for the treatment of hematological malignancies.
详细描述
Patients eligible to receive CAR T-cell therapy for FDA-approved indications in hematological malignancies will be enrolled in this study on the day of CAR T-cell infusion. Patients will be followed until they develop grade 1 or higher CRS and/or ICANS. On developing these syndromes, siltuximab will be administered with close monitoring and follow-up for resolution of symptoms. If symptoms continue to worsen, then an additional dose of siltuximab will be given. If the symptoms leading to CRS do not resolve, then rescue tocilizumab will be administered. The study's primary endpoint is to assess the response rate of siltuximab in the resolution of CRS within 14 days. The study's secondary endpoint is to assess the response rate of siltuximab in the resolution of ICANS, the safety of siltuximab, and the overall response rate of CAR T-cell therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Patients who are planned to receive chimeric antigen receptor T-cell therapy as per the United States Food and Drug Agency (USFDA) approved indications for Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma (MCL), Follicular lymphoma (FL), Primary mediastinal large B-cell lymphoma (PMBCL), High grade B-cell lymphoma, DLBCL arising from follicular lymphoma, Multiple myeloma and B-cell precursor acute lymphoblastic leukemia
- •Patients with hepatitis C virus (HCV) can be included if they have completed therapy for hepatitis C with undetectable HCV RNA viral load.
- •Patients with Hepatitis B can be included if they are on suppressive therapy for hepatitis B infection and with no detectable viral load.
- •Adequate organ function as defined below unless attributed to disease involvement.Acceptable window for assessing adequate organ function is 7 days to 30 days before planned CAR T-cell infusion with day 0 as the planned day of CAR T-cell infusion.Adequate liver function (bilirubin < 2mg/dL, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) <3 x ULN), adequate kidney function (crcl > 30ml/min using Cockcroft-Gault, based on actual weight) and adequate hematological parameters (Absolute neutrophil count ≥ 1,000/µL, Hemoglobin > 8, Platelet Count ≥ 50,000/ µL)
- •Patients able to tolerate washout periods for therapies prior to CAR T-cell infusion. Systemic therapy: Washout period is 2 weeks prior to CAR T-cell infusion. Radiation therapy: Washout period is 1 week prior to CAR T-cell infusion. Corticosteroids: The washout period is 5 days prior to CAR T-cell infusion.
- •A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- •For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 months after infusion of siltuximab.
- •For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
- •Willing and able to participate in all required evaluations and procedures in this study protocol including receiving intravenous administration of the investigational product and being admitted, when required, for at least 24 hours during investigational product administration.
排除标准
- •Subjects requiring ongoing daily corticosteroid therapy at a dose of > 10 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)
- •Pregnant women are excluded from this study.
- •Evidence of ongoing systemic bacterial, or fungal or viral infection, except localized fungal infection of skin or nails.
- •Patients with ongoing or past HIV infection.
研究组 & 干预措施
Siltuximab
Patients who experience CRS/ICANS will receive this treatment
干预措施: Siltuximab (Drug)
结局指标
主要结局
Participants with a complete response for cytokine release syndrome (CRS)
时间窗: Baseline through 14 days
Participants who achieve a resolution of CRS. Resolution of CRS is defined as absence of symptoms leading to diagnosis of CRS for 24 hours.
次要结局
- Participants with a response for Immune effector Cell Associated Neurotoxicity Syndrome (ICANS)(Baseline through 28 days)
- Participants experiencing adverse events from Siltuximab(Baseline through 28 days)
- Participants with response to CAR T-cell therapy(Baseline through day 90)
研究者
Aditi Saha, MD
Assistant Professor
University of Alabama at Birmingham