Phase 1b Study Evaluating the Safety and Efficacy of Autologous CD30.CAR-T in Combination With PD-1 Checkpoint Inhibitor (Nivolumab) in Relapsed or Refractory Classical Hodgkin Lymphoma Patients After Failure of Frontline Therapy (ACTION)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 15
- 试验地点
- 5
- 主要终点
- Safety of autologous CD30.CAR-T in combination with nivolumab
研究概览
简要总结
This is a Phase 1b, multicenter, open-label, single arm study to evaluate the safety and efficacy of the combination therapy, CD30.CAR-T and the programmed cell death protein-1 (PD-1) checkpoint inhibitor, nivolumab, in patients aged 12 years of age and above with relapsed or refractory classical Hodgkin lymphoma (cHL) following failure of standard frontline therapy.
详细描述
Upon successful leukapheresis to produce CD30.CAR-T cells, patients will enter the treatment phase of the study. Treatments will include 4 cycles of nivolumab and CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy). Patients will then enter the post-treatment follow-up phase of the study, whereby patients will undergo either autologous stem cell transplant or continue to receive up to 6 additional treatment cycles of nivolumab. Patients will be followed for response assessments and safety monitoring until end of study (EOS); approximately 3 years after leukapheresis. Long-term follow-up will continue with additional safety monitoring and survival for up to 15 years after Leukapheresis.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients who are 12 years of age and above
- •Relapsed or refractory CD30+ cHL following failure of a standard frontline chemotherapy
- •At least 1 lesion, which must be fluordeoxyglucose positron emission tomography (FDG-PET) avid and measurable by PET-CT scan
- •Adequate laboratory parameters including hematologic, renal, hepatic, and coagulation function
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, or equivalent either Karnofsky performance status (for patients ≥ 16 years of age) or Lansky performance status (for patients < 16 years of age)
- •Anticipated life expectancy > 12 weeks
- •No active infections including COVID 19 at Screening
排除标准
- •Evidence of lymphomatous involvement of the central nervous system (CNS)
- •Presence of clinically relevant or active seizure disorder, stroke, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
- •Symptomatic cardiovascular disease: Class III or IV according to the New York Heart Association (NYHA) Functional Classification
- •Active uncontrolled bleeding or a known bleeding diathesis
- •Inadequate pulmonary function defined as oxygen saturation by pulse oximetry < 90% on room air
- •Echocardiogram (ECHO) or Multi-gated Acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) < 45%
- •Prior receipt of salvage therapy, for relapsed or refractory cHL, including allogeneic or ASCT
- •Prior receipt of investigational CD30.CAR-T cells
- •Receiving any investigational agents or any tumor vaccines
- •Receiving any live/attenuated vaccines
- •Ongoing treatment with immunosuppressive drugs or chronic systemic corticosteroids
- •Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments
- •Previous history of known or suspected autoimmune disease within the past 5 years
- •Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- •Evidence of human immunodeficiency virus (HIV) infection
- •Evidence of active viral infection with hepatitis B virus (HBV)
- •Evidence of active viral infection with hepatitis C virus (HCV)
- •Active second malignancy or history of another malignancy within the last 3 years
- •History of hypersensitivity reactions to murine protein-containing products or other product excipients
- •Any allergic or adverse reaction to nivolumab, fludarabine, or bendamustine that precludes treatment with these agents
- •History of a significant irAE from prior immune checkpoint inhibitor therapy
研究组 & 干预措施
Nivolumab and CD30.CAR-T
Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).
干预措施: Nivolumab (Drug)
Nivolumab and CD30.CAR-T
Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).
干预措施: Autologous CD30.CAR-T (Drug)
Nivolumab and CD30.CAR-T
Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).
干预措施: Fludarabine (Drug)
Nivolumab and CD30.CAR-T
Study treatment will include 4 cycles of nivolumab and a single CD30.CAR-T infusion (preceded by lymphodepletion chemotherapy of Fludarabine and Bendamustine).
干预措施: Bendamustine (Drug)
结局指标
主要结局
Safety of autologous CD30.CAR-T in combination with nivolumab
时间窗: From first dose of nivolumab (Cycle 1) to end of nivolumab Cycle 4 (each cycle is 28 days)
DLT
次要结局
- Progression-free survival(Through study completion, an average of 3 years from Leukapheresis)
- Overall response rate(Through study completion, an average of 3 years from Leukapheresis)
- Anti-tumor activity using CR rate of autologous CD30.CAR-T in combination with nivolumab(Up to end of 10 weeks post-CD30.CAR-T treatment)
- Duration of response(Through study completion, an average of 3 years from Leukapheresis)