NCT02776813已完成1 期
Phase 1 Study of ACTR087, Autologous T Lymphocytes Expressing Antibody Coupled T-cell Receptors (CD16V-41BB-CD3ζ), in Combination With Rituximab, in Subjects With Relapsed or Refractory CD20-Positive B-Cell Lymphoma
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 14
- 主要终点
- Safety as assessed by and adverse events, laboratory assessments and physical examinations
研究概览
简要总结
This is a phase 1, multi-center, single-arm, open-label study evaluating the safety and efficacy of an autologous T-cell product expressing ACTR in combination with rituximab in subjects with refractory or relapsed CD20+ B-cell lymphoma.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent obtained prior to study procedures
- •Histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy:
- •DLBCL, regardless of cell of origin or underlying molecular genetics
- •Biopsy-confirmed CD20+ expression of the underlying malignancy by immunohistochemical staining or flow cytometry between the most recent dose of an anti-CD20 monoclonal antibody (mAb) and study enrollment
- •At least 1 measurable lesion on imaging. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- •Must have received adequate prior therapy for the underlying CD20+ B-cell lymphoma, defined as an anti-CD20 mAb in combination with an anthracycline-containing chemotherapy regimen (i.e. chemo-immunotherapy) and at least one of the following:
- •biopsy-proven refractory disease after frontline chemo-immunotherapy
- •relapse within 1 year from frontline chemo-immunotherapy and ineligible for autologous hematopoietic stem cell transplant (auto-HSCT)
- •For subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT
- •For subjects with TH-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT. At least 1 prior regimen with an anti-CD20 mAb in combination with chemotherapy is required following documented transformation
- •For subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
- •Karnofsky performance scale ≥ 60%
- •Life expectancy of at least 6 months
- •ANC > 1000/µL
- •Platelet count > 50,000/µL
- •For women of childbearing potential (defined as physiologically capable of becoming pregnant), agreement to use of highly effective contraception for at least 1 year following ACTR087 infusion. For men with partners of childbearing potential, agreement to use effective barrier contraception for at least 1 year following ACTR087 infusion
排除标准
- •Known active central nervous system (CNS) involvement by malignancy. Subjects with prior CNS involvement with their lymphoma must have completed effective treatment of their CNS disease at least 3 months prior to enrollment with no evidence of disease clinically and at least stable findings on relevant CNS imaging
- •Prior treatment as follows:
- •alemtuzumab within 6 months of enrollment
- •fludarabine, cladribine, or clofarabine within 3 months of enrollment
- •external beam radiation within 2 weeks of enrollment
- •mAb (including rituximab) within 2 weeks of enrollment
- •other lymphotoxic chemotherapy (including steroids except as below) within 2 weeks of enrollment
- •experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy
- •Serum creatinine ≥ 1.5 X age-adjusted upper limits of normal (ULN)
- •Pulse oximetry < 92% on room air
- •Direct bilirubin ≥ 3.0 mg/dL (50 mmol/L)
- •Alanine transaminase (ALT) ≥ 3 times the ULN, unless determined to be directly due to lymphoma.
- •Aspartate transaminase (AST) ≥ 3 times the ULN, unless determined to be directly due to lymphoma
- •Class III or IV heart failure as defined by the New York Heart Association (NYHA), history of cardiac angioplasty or stenting, documented myocardial infarction or unstable angina within 6 months prior to enrollment, cardiac ejection fraction of < 45%, or other clinically significant cardiac disease
- •Clinical history of, prior diagnosis of, or overt evidence of autoimmune disease, regardless of severity
- •Clinically significant active infection, in the judgment of the investigator
- •Pregnancy (negative serum pregnancy test to be obtained within 6 days prior to enrollment for subjects of childbearing potential)
- •Breastfeeding
- •Primary immunodeficiency
- •Seropositive for Human Immunodeficiency Virus (HIV) 1 or HIV 2, or positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody
- •Will need or has needed active treatment of a second malignancy within the prior 3 years before enrollment, other than FL, non-melanoma skin cancers, localized prostate cancer treated with curative intent, or cervical carcinoma in situ
- •Is unable to receive any of the agents used in this study due a history of severe immediate hypersensitivity reaction (e.g. hypersensitivity to dimethyl sulfoxide (DMSO))
- •History of prior allogeneic HSCT
- •History of Richter's transformation from CLL
- •Prior infusion of a genetically modified therapy
结局指标
主要结局
Safety as assessed by and adverse events, laboratory assessments and physical examinations
时间窗: 24 months
Safety as assessed by determination of the recommended phase 2 dose (RP2D)
时间窗: 24 months
Safety as assessed by dose limiting toxicities (DLTs)
时间窗: 28 days
Safety as assessed by determination of the maximum tolerated dose (MTD)
时间窗: 24 months
Safety as assessed by mini-mental state examination (MMSE)
时间窗: 24 months
次要结局
- Overall response rate(24 months)
- Duration of response(24 months)
- Overall survival(60 months)
- Progression free survival(24 months)
研究者
研究点 (14)
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