NCT05607420招募中1 期
Open-label Dose-finding and Dose-expansion Study to Evaluate the Safety, Expansion, Persistence, and Clinical Activity of UCART20x22 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (B-NHL)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 10
- 主要终点
- Dose finding and expansion parts: Incidence of adverse events/serious adverse events/dose limiting toxicity [Safety and Tolerability]
研究概览
简要总结
First-in-human, open-label, dose-finding and dose-expansion study of UCART20x22 administered intravenously in subjects with relapsed or refractory B-Cell Non-Hodgkin Lymphoma (B-NHL). The purpose of this study is to evaluate the safety and clinical activity of UCART20x22 and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Relapsed or refractory (R/R) mature B-NHL per 2016 WHO criteria and positive for CD20 and/or CD22
- •Subjects with NHL subtypes defined by WHO:
- •Dose-Finding Part: R/R mature B-NHL (except chronic lymphocytic leukemia/small lymphocytic leukemia [CLL/SLL], Richter's transformation from prior CLL/SLL, Burkitt's lymphoma, and Waldenstrom's macroglobulinemia)
- •Dose-Expansion Part: R/R LBCL, defined as:
- •i. DLBCL; ii. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; iii. Transformed FL or transformed marginal zone lymphoma (MZL); iv. Follicular lymphoma Grade 3B
- •R/R disease after at least 2 lines of prior treatment, which must have included:
- •An Anti-CD20 MoAb and an anthracycline for DLBCL, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, primary mediastinal large B-cell lymphoma (PMBCL), or transformed FL or MZL
- •An alkylating agent in combination with an anti-CD20 MoAb for FL
- •An anthracycline or bendamustine-containing chemotherapy regimen and a Bruton's tyrosine kinase (BTK) inhibitor for mantle cell lymphoma (MCL)
- •Autologous anti-CD19 CAR T-cell therapy, if approved and available for the indicated lymphoma subtype, unless the subject is unable or is ineligible to receive approved autologous anti-CD19 CAR T-cell therapy (e.g., fail leukapheresis or manufacture, unable to wait for manufacture, CD19 negative disease, etc.)
- •Autologous hematopoietic stem cells must be available prior to the start of the LD regimen if the subject is considered high-risk for prolonged hematologic toxicity.
排除标准
- •Prior use of an investigational product (except for cell or gene therapies and MoAbs) within 5 half-lives or within 14 days, whichever is shorter, prior to start of LD regimen
- •Previous approved therapy including chemotherapy, biologic (except MoAbs), or targeted therapy for R/R B-NHL with 5 half-lives or within 14 days, whichever is shorter, prior to start of the LD regimen
- •> 4 lines of therapy R/R B-NHL prior to start of the LD regimen.
- •Prior MoAb therapy (approved or investigational) within 30 days prior to start of LD
- •Prior systemic immunostimulatory agent within 3 half-lives prior to start of the LD regimen
- •Prior cell or gene therapy (approved or investigational) within 6 months of the start of LD
- •Prior cell or gene therapy (approved or investigational) targeting both CD20 and CD22
- •Autologous HSCT infusion within 6 weeks of the start of LD
- •Allogeneic HSCT within 3 months of the start of LD, or donor lymphocyte infusion within 6 weeks of the start of LD
- •Active acute or chronic graft versus host disease (GvHD). Subjects should be off all immunosuppressive therapies for at least 6 weeks prior to start of LD
- •Radiotherapy within 8 weeks (except for palliative radiotherapy for specific on-target lesions) (prior to start of LD regimen)
- •Evidence of active central nervous system (CNS) lymphoma or previous CNS involvement of R/R B-NHL
- •Presence of an active and clinically relevant CNS disorder
- •Daily treatment with >20 mg prednisone or equivalent
- •Known active infection, or reactivation of a latent infection, whether bacterial or viral, fungal, mycobacterial, or other pathogens
- •History of hypersensitivity to alemtuzumab
- •History of neutralizing anti-drug antibody against alemtuzumab
- •Any known uncontrolled cardiovascular disease within 3 months of enrollment
- •Subjects requiring immunosuppressive treatment
- •Major surgery within 28 days prior to start of LD
- •Evidence of another uncontrolled malignancy within 2 years prior to Screening (except in situ nonmelanoma skin cell cancers and/or carcinoma in-situ of the cervix)
研究组 & 干预措施
Dose finding part
Experimental
UCART20x22 tested at several dose levels until the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) is identified.
Dose expansion part: UCART20x22 administered at the RP2D determined during the dose finding part
干预措施: UCART20x22 (Biological)
Dose finding part
Experimental
UCART20x22 tested at several dose levels until the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) is identified.
Dose expansion part: UCART20x22 administered at the RP2D determined during the dose finding part
干预措施: CLLS52 (Biological)
结局指标
主要结局
Dose finding and expansion parts: Incidence of adverse events/serious adverse events/dose limiting toxicity [Safety and Tolerability]
时间窗: From study entry through month 12
Incidence, nature and severity of adverse events and serious adverse events in relation to UCART20x22 and/or lymphodepletion
Dose finding part: Occurrence of Dose Limiting Toxicities (DLTs)
时间窗: Up to Day 28 post UCART20x22 infusion
次要结局
- Investigator assessed overall response rate (ORR) according to Lugano Response Criteria for Malignant Lymphoma(At Day 28, Day 84, Month 6, Month 9, Month 12)
- Progression-free survival (PFS)(From the first day of any study treatment to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 12)
- Duration of Response(From achievement of the initial response to disease relapse/progression or death from any cause, assessed up to Month 12)
- Overall survival(From initiation of any study treatment to death from any cause, assessed up to Year 15)
研究者
研究点 (10)
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