A Single-arm, Multicenter, Open-label, Phase I/II Trial of Allo-QuadCAR01-T, an Allogeneic CAR-T-cell Therapy Targeting CD19 and CD20, for the Treatment of Relapsed or Refractory B-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 178
- 试验地点
- 16
- 主要终点
- Incidence of AEs defined as DLTs
研究概览
简要总结
This study is testing Allo-QuadCAR01-T, a new off-the-shelf CAR-T therapy for people with hard-to-treat B-cell cancers. Unlike current CAR-T treatments that use a patient's own cells, this therapy uses donor cells that are ready to use, which can save time and reduce costs. It targets two proteins, CD19 and CD20, to lower the chance of relapse and uses gene editing to make it safer. The trial has three parts: first to find a safe dose, then to confirm it, and finally to test how well it works in patients with diffuse large B-cell lymphoma (DLBCL). Patients will get one infusion after chemotherapy to prepare their body. The main goal is to check safety and see how many patients have a complete response by Week 13. About 160 patients will take part, and researchers will follow them for up to 15 years.
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
- •Adults 18 years or older.
- •Diagnosed with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukemia (CLL).
- •Must have received at least 2 prior lines of therapy.
- •ECOG performance status 0-1 (able to carry out daily activities).
- •Adequate organ function (heart, liver, kidneys).
- •HLA B/C match with donor cells.
- •No active uncontrolled infections.
排除标准
- •Active CNS involvement (including PCNSL) in dose escalation cohorts; may be allowed in later cohorts with Sponsor approval.
- •Prior CAR-T within 3 months of screening, or ≥Grade 3 ICAHT from prior CAR-T.
- •Autologous stem cell transplant within 3 months.
- •Prior allogeneic stem cell transplant or solid organ transplant.
- •Prior therapy with dual CD19/CD20 CAR-T.
- •Severe hypersensitivity to trial agents or similar compounds.
- •History of GvHD or post-transplant lymphoproliferative disorder.
- •Presence of La/SS-B autoantibodies or related autoimmune diseases.
- •Other malignancy that may interfere with trial, except:
- •Curatively treated basal/squamous skin cancer or cervical carcinoma in situ
- •Low-grade, early-stage prostate cancer (Gleason ≤6, Stage 1-2) with no therapy needed
- •Adjuvant endocrine therapy for non-metastatic breast cancer (≥2 years)
- •Any other curatively treated malignancy in remission ≥2 years
- •Active viral infection within 1 week of screening, or serious bacterial/fungal infection.
- •Hemorrhagic cystitis.
- •Active neuro-autoimmune disease (e.g., MS, Guillain-Barré, ALS).
- •Active or residual HBV, HCV, or syphilis.
- •Active HIV. History of HIV may be eligible with Sponsor approval if:
- •Neurological disorders within 6 months (e.g., stroke, dementia, Parkinson's, cerebellar disease, CNS autoimmune disease).
- •Significant cardiac disease within 6 months (e.g., MI, stent, unstable angina).
- •Primary immunodeficiency or autoimmune disease requiring systemic treatment within 1 year (unless stable and Sponsor-approved).
- •Unresolved ≥Grade 2 non-hematologic toxicity from prior therapy (except neuropathy up to Grade 2).
- •Systemic immunosuppression within 28 days.
- •Last systemic lymphoma/CLL therapy (standard or investigational) within 28 days or 5 half-lives.
- •Major surgery within 14 days.
- •Local radiation within 28 days.
- •Live vaccination within 28 days.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Allo-QuadCAR01-T
Phase Ia (Escalation): Participants with relapsed or refractory B-cell malignancies will receive lymphodepleting chemotherapy followed by a single infusion of Allo-QuadCAR01-T.
Phase Ib (Expansion): After dose escalation, additional participants with relapsed or refractory B-cell lymphoma will receive lymphodepleting chemotherapy followed by a single infusion of Allo-QuadCAR01-T at one or more tolerable dose levels from Phase Ia.
Phase II: Participants with relapsed or refractory DLBCL will receive lymphodepleting chemotherapy, followed by a single infusion of Allo-QuadCAR01-T at the recommended Phase II dose. The primary endpoint is complete response rate at Week 13, with secondary endpoints including duration of response, progression-free survival, and overall survival.
干预措施: Allo-QuadCAR01-T (Drug)
Allo-QuadCAR01-T
Phase Ia (Escalation): Participants with relapsed or refractory B-cell malignancies will receive lymphodepleting chemotherapy followed by a single infusion of Allo-QuadCAR01-T.
Phase Ib (Expansion): After dose escalation, additional participants with relapsed or refractory B-cell lymphoma will receive lymphodepleting chemotherapy followed by a single infusion of Allo-QuadCAR01-T at one or more tolerable dose levels from Phase Ia.
Phase II: Participants with relapsed or refractory DLBCL will receive lymphodepleting chemotherapy, followed by a single infusion of Allo-QuadCAR01-T at the recommended Phase II dose. The primary endpoint is complete response rate at Week 13, with secondary endpoints including duration of response, progression-free survival, and overall survival.
干预措施: Cyclophosphamide (Non-IMP, Lymphodepletion) (Other)
Allo-QuadCAR01-T
Phase Ia (Escalation): Participants with relapsed or refractory B-cell malignancies will receive lymphodepleting chemotherapy followed by a single infusion of Allo-QuadCAR01-T.
Phase Ib (Expansion): After dose escalation, additional participants with relapsed or refractory B-cell lymphoma will receive lymphodepleting chemotherapy followed by a single infusion of Allo-QuadCAR01-T at one or more tolerable dose levels from Phase Ia.
Phase II: Participants with relapsed or refractory DLBCL will receive lymphodepleting chemotherapy, followed by a single infusion of Allo-QuadCAR01-T at the recommended Phase II dose. The primary endpoint is complete response rate at Week 13, with secondary endpoints including duration of response, progression-free survival, and overall survival.
干预措施: Fludarabine (Non-IMP, Lymphodepletion) (Other)
结局指标
主要结局
Incidence of AEs defined as DLTs
时间窗: At the end of cycle 1 (in total 28 days, given no treatment interruptions)
Incidence and intensity of adverse events (AEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), tumor lysis syndrome, and graft versus host disease (GvHD), which will be graded according to widely accepted specialized criteria
To determine the maximum tolerated dose (MTD)
时间窗: At the End of Cycle 1 (in total 28 days, given no treatment interruptions)
MTD
To determine the incidence of dose-limiting toxicities (DLT)
时间窗: At the end of cycle 1 (in total 28 days, given no treatment interruptions)
Incidence of DLTs
Phase 2: Complete response rate (CRR)
时间窗: Up to week 13
Complete remission rate is defined as the proportion of participants with complete remission, per international working group (IWG) Lugano classification, as assessed by the investigator.
次要结局
- Pharmacokinetics of Allo-QuadCAR01-T in PB in patients after infusion of Allo-QuadCAR01-T(Up to 24 months)
- To investigate the impact of Allo-QuadCAR01-T on MRD(Up to 24 months)
- To evaluate immunogenicity against Allo-QuadCAR01-T(Up to 24 months)
- To evaluate host immune cell depletion and reconstitution resulting from LD(Up to 24 months)
- Overall Response Rate (ORR)(Up to 24 months)
- Progression-Free Survival (PFS)(Up to 24 months)
- Duration of Response (DOR)(Up to 24 months)
- Overall Survival (OS)(Up to 24 months)
- Time to Next Treatment (TTNT)(Up to 24 months)