NCT04150913已完成2 期
A Phase 2 Trial of Anakinra for the Prevention of CAR-T Cell Mediated Neurotoxicity
Marcela V. Maus, M.D.,Ph.D.2 个研究点 分布在 1 个国家目标入组 15 人开始时间: 2020年10月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Rate of Neurotoxicity as Per CTCAE v4.03 Criteria
研究概览
简要总结
This research study is studying the combination of anakinra and axicabtagene ciloleucel to reduce the occurrence of the side effects Cytokine Release Syndrome (CRS) and neurologic toxicities with relapsed or refractory Non-Hodgkin lymphoma (NHL).
- Relapsed NHL is the condition of returned Non-Hodgkin lymphoma.
- Refractory NHL is the condition of previous treatment resistant Non-Hodgkin lymphoma.
- Cytokine Release Syndrome (CRS) is a group of side effect symptoms that can include nausea, headache, rapid heartbeat, shortness of breath, kidney damage, and rash.
- Neurologic toxicity is nervous system disorder characterized by confusion
This research study involves two drugs:
- Anakinra
- Axicabtagene Ciloleucel.
详细描述
This Phase 2, single center, open-label research study is studying the combination of Anakinra and Axicabtagene Ciloleucel to reduce the occurrence of the side effects Cytokine Release Syndrome (CRS) and neurologic toxicities in people with relapsed or refractory Non-Hodgkin lymphoma (NHL).
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
-
This research study involves two drugs:
-
Anakinra
-
Axicabtagene Ciloleucel
-
A total of 20 participants are anticipated to be enrolled to this trial
-
The U.S. Food and Drug Administration (FDA) has not approved anakinra for use in treatment of Non-Hodgkin lymphoma (NHL).
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
- •Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
- •At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma
- •Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- •At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy however steroids only require a 7-day washout. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc).
- •Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia)
- •Age 18 or older
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •ANC ≥1000/uL
- •Platelet count ≥75,000/uL
- •Absolute lymphocyte count ≥100/uL
- •Adequate renal, hepatic, pulmonary and cardiac function defined as:
- •Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
- •Serum ALT/AST ≤2.5 ULN
- •Total bilirubin ≤1.5 mg/dl, except in subjects with Gilbert's syndrome.
- •Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion, and no clinically significant ECG findings
- •No clinically significant pleural effusion
- •Baseline oxygen saturation >92% on room air
- •Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential) Ability to understand and the willingness to sign a written informed consent document.
- •Exclusion Criteria
- •History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
- •History of Richter's transformation of CLL
- •Autologous stem cell transplant within 6 weeks of planned axicabtagene ciloleucel infusion
- •History of allogeneic stem cell transplantation
- •Prior CD19 targeted therapy with the exception of subjects who received axicabtagene ciloleucel in this study and are eligible for re-treatment
- •Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
- •History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
- •Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
- •History of HIV infection or acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines.
- •Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted
- •Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
- •History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
- •Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
- •History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
- •Expected or possible requirement for urgent therapy within 6 weeks due to ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis syndrome)
- •Primary immunodeficiency
- •History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
- •Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
- •History of severe immediate hypersensitivity reaction to any of the agents used in this study
- •Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen
- •Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential
- •Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of axicabtagene ciloleucel
- •In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
- •History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
排除标准
- 未提供
研究组 & 干预措施
Anakinra and Axicabtagene Ciloleucel
Experimental
Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment.
-
Screening
-
Enrollment/Leukapheresis period
-
Bridging therapy (if applicable)
-
Lymphodepleting chemotherapy period
-
Investigational Product (IP) treatment period
-
Anakinra
-
Axicabtagene Ciloleucel
-
Post treatment assessment period
-
Long term follow-up period
干预措施: Anakinra (Drug)
Anakinra and Axicabtagene Ciloleucel
Experimental
Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment.
-
Screening
-
Enrollment/Leukapheresis period
-
Bridging therapy (if applicable)
-
Lymphodepleting chemotherapy period
-
Investigational Product (IP) treatment period
-
Anakinra
-
Axicabtagene Ciloleucel
-
Post treatment assessment period
-
Long term follow-up period
干预措施: Axicabtagene Ciloleucel (Drug)
结局指标
主要结局
Rate of Neurotoxicity as Per CTCAE v4.03 Criteria
时间窗: 30 Days
The incidence of grade 2+ neurotoxicity is reported below and was assessed using CTCAE (Common Terminology Criteria for Adverse Events) v4.04 criteria. Neurotoxicity is a serious side effect of cancer treatments that can impact the central and peripheral nervous systems. Neurotoxicity manifestations vary and can include confusion, obtundation, seizures, hallucinations, aphasia, ataxia, and more rarely, profound cerebral edema.
次要结局
- Objective Response Rate(24 Months)
- Duration of Response(first objective response to disease progression death regardless of cause up 24 Months)
- Progression-free Survival(infusion date to the date of disease progression or death from any cause up 24 Months)
- Overall Survival(time from axicabtagene ciloleucel infusion to the date of death or analysis data cutoff date will be censored at last contact date up to 24 months.)
- Number of Participants With Adverse Events CTCAE Version 4.03 Grade 3 or Higher(24 Months)
- Rate of Cytokine Release Syndrome (CRS) as Per Lee 2014 for CRS(Within 30 days after infusion)
研究者
Marcela V. Maus, M.D.,Ph.D.
Sponsor-Investigator
Massachusetts General Hospital
研究点 (2)
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