A Single-Center Phase I Clinical Trial of Dual-Targeted Umbilical Cord Blood CAR-T Cells Against CD19 and CD22 for the Treatment of Relapsed or Refractory Acute B-Cell Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Incidence and Severity of Dose-Limiting Toxicity (DLT)
研究概览
简要总结
This investigator-initiated, prospective, single-arm, phase I dose-escalation trial aims to evaluate the safety and tolerability of anti-CD19/CD22 dual-target cord blood-derived CAR-T cells in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia who have failed prior therapies, with the goal of reducing antigen-escape relapse and overcoming poor autologous T-cell fitness through the use of universally available umbilical cord blood T cells.
详细描述
Patients with relapsed/refractory B-cell acute lymphoblastic leukemia who meet eligibility criteria will receive fludarabine (30 mg/m²/d) and cyclophosphamide (300 mg/m²/d) for three consecutive days as lymphodepleting conditioning, followed by a single intravenous infusion of anti-CD19/CD22 dual-target cord blood-derived CAR-T cells. Dose assignment follows a "3+3" escalation design across three dose levels (4×10⁶, 8×10⁶, and 12×10⁶ CAR-T/kg, ±20%). Dose-limiting toxicity will be assessed during the first 14 days post-infusion to determine the maximum tolerated dose. After CAR-T infusion, patients will be monitored for safety and efficacy at protocol-specified time points through 3 months, with long-term follow-up continuing up to 15 years post-infusion. A total of 18 patients will be enrolled.
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
- •The patient or their legally authorized guardian has signed the informed consent form (ICF), indicating understanding of the purpose and procedures of this clinical trial and willingness to participate.
- •Age between 18 and 75 years, male or female.
- •Diagnosis of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) according to the Chinese Guidelines for Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2024 edition).
- •Leukemic cells confirmed to express CD19 and/or CD22 by flow cytometry.
- •ECOG performance status 0-
- •Life expectancy ≥12 weeks.
- •Adequate organ function at screening, meeting all of the following laboratory criteria:
- •Hematology: absolute neutrophil count (ANC) ≥1×10⁹/L; absolute lymphocyte count (ALC) ≥0.3×10⁹/L; platelet count ≥20×10⁹/L; hemoglobin ≥60 g/L.
- •Hepatic function: ALT and AST ≤2.5× upper limit of normal (ULN); total bilirubin ≤1.5× ULN.
- •Renal function: creatinine clearance (CrCl) ≥40 mL/min (by Cockcroft-Gault formula).
- •Coagulation: fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5× ULN; prothrombin time (PT) ≤1.5× ULN.
- •Oxygen saturation >91%.
- •Left ventricular ejection fraction (LVEF) ≥50%.
- •The subject and their spouse agree to use effective contraceptive measures (excluding rhythm method) from ICF signing through 1 year after CAR-T cell infusion.
排除标准
- •Active graft-versus-host disease (GVHD) or autoimmune disease requiring long-term immunosuppressive therapy.
- •Use of therapeutic doses of corticosteroids (defined as prednisone or equivalent >20 mg/day) within 7 days prior to screening. Physiologic replacement, topical, and inhaled steroids are permitted.
- •Hypertension not controllable with medication.
- •Severe cardiac disease, including but not limited to: unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA class ≥III), or severe arrhythmia.
- •Unstable systemic disease as judged by the investigator, including but not limited to: severe hepatic, renal, or metabolic disease requiring medication.
- •Malignancy other than B-ALL within 5 years prior to screening, except for adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, localized prostate cancer after radical surgery, or ductal carcinoma in situ of the breast after radical surgery.
- •History of solid organ transplantation.
- •Planned surgery within 2 weeks after study treatment (subjects scheduled for local anesthesia surgery may participate).
- •Receipt of other interventional investigational drugs within 1 month prior to ICF signing.
- •Uncontrolled active infection.
- •Positive for HBsAg, or positive for HBcAb with detectable HBV DNA in peripheral blood; positive for HCV antibody with detectable HCV RNA; positive for HIV antibody; positive for CMV DNA; positive for syphilis serology.
- •Pregnant or breastfeeding women.
- •Psychiatric illness, consciousness disorder, or central nervous system disease.
- •Other conditions deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
Anti-CD19/CD22 Dual-Target Cord Blood CAR-T Cells
A single intravenous infusion of anti-CD19/CD22 dual-target umbilical cord blood-derived CAR-T cells administered on Day 0, following lymphodepleting chemotherapy with fludarabine (30 mg/m²/day) and cyclophosphamide (300 mg/m²/day) for three consecutive days. Dose escalation follows a 3+3 design across three dose levels (4.0×10⁶, 8.0×10⁶, and 12.0×10⁶ CAR-T/kg, ±20%). All subjects receive the same investigational product; no comparator arm is included.
干预措施: Anti-CD19/CD22 Dual-Target Cord Blood CAR-T Cells (Biological)
Anti-CD19/CD22 Dual-Target Cord Blood CAR-T Cells
A single intravenous infusion of anti-CD19/CD22 dual-target umbilical cord blood-derived CAR-T cells administered on Day 0, following lymphodepleting chemotherapy with fludarabine (30 mg/m²/day) and cyclophosphamide (300 mg/m²/day) for three consecutive days. Dose escalation follows a 3+3 design across three dose levels (4.0×10⁶, 8.0×10⁶, and 12.0×10⁶ CAR-T/kg, ±20%). All subjects receive the same investigational product; no comparator arm is included.
干预措施: Fludarabine (Drug)
Anti-CD19/CD22 Dual-Target Cord Blood CAR-T Cells
A single intravenous infusion of anti-CD19/CD22 dual-target umbilical cord blood-derived CAR-T cells administered on Day 0, following lymphodepleting chemotherapy with fludarabine (30 mg/m²/day) and cyclophosphamide (300 mg/m²/day) for three consecutive days. Dose escalation follows a 3+3 design across three dose levels (4.0×10⁶, 8.0×10⁶, and 12.0×10⁶ CAR-T/kg, ±20%). All subjects receive the same investigational product; no comparator arm is included.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Incidence and Severity of Dose-Limiting Toxicity (DLT)
时间窗: Within 14 days after CAR-T cell infusion
DLT is defined as treatment-related adverse events occurring within 14 days post-infusion. Non-hematologic DLT: Grade ≥3 toxicity not reducible to ≤ Grade 1 within 72 hours. Hematologic DLT: Grade 4 toxicity (excluding lymphopenia) persisting \>21 days, not attributable to underlying disease. Predefined exclusion criteria include tumor lysis syndrome, electrolyte disturbances, hypogammaglobulinemia, transient laboratory abnormalities, febrile neutropenia, and others per protocol. CRS/ICANS graded per ASTCT 2019, aGVHD per modified Glucksberg, other AEs per CTCAE v5.0.
次要结局
- Objective Response Rate (ORR)(1 and 3 months post-infusion)
- Minimal Residual Disease (MRD) Negativity Rate(1 and 3 months post-infusion)
- Complete Remission (CR) Rate(1 and 3 months post-infusion)
- Progression-Free Survival (PFS)(From infusion up to 24 months)
- Overall Survival (OS)(From infusion up to 24 months)
- CAR-T Cell Expansion and Persistence(Up to 90 days post-infusion)
- CAR-T Cell Expansion and Persistence(At 3 and 6 months)
研究者
Jin Wang
chief physician, MD, PhD
Ruijin Hospital