NCT06287528招募中1 期
A Phase I Trial of CD19-targeted Chimeric Antigen Receptor (CAR) T Cells That Constitutively Secrete Interleukin 18 (19-28z/IL-18) in Patients With Relapsed or Refractory (R/R) Acute Lymphoblastic Leukemia (ALL)
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
- 18
- 试验地点
- 14
- 主要终点
- Toxicity as determined by CTCAE, version 5.0
研究概览
简要总结
Participants will have a sample of their white blood cells, called T cells, collected using a procedure called leukapheresis. The collected T cells will be sent to a laboratory to be changed (modified) to become 19-28z/IL-18, the CAR T-cell therapy that participants will receive during the study. Making the participants' study therapy will take about 2-4 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 17 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have R/R ALL meeting one of the following criteria:
- •For Philadelphia chromosome (Ph) negative B-ALL: Refractory or relapsed disease to at least 1 prior multiagent systemic chemotherapy regimen that included both induction and consolidation therapy
- •For Philadelphia chromosome (Ph) positive B-ALL: patients must have exhibited persistent or progressive disease following at least 1 prior second- or third-generation tyrosine kinase inhibitor
- •Signed informed consent form (ICF) prior to any study procedures
- •Age: The first 3 patients enrolled into the study will be ≥ 17 years of age at time of enrollment. If a DLT is observed, the additional 3 patients in this cohort will also be ≥ 17 years of age. Additional patients will be ≥12 years of age at time of enrollment.
- •Documentation of CD19 positivity on leukemia blasts if prior anti-CD19 treatment
- •History of prior allogeneic hematopoietic stem cell transplant (HSCT) is allowed if ≥3 months from time of enrollment and no evidence of acute or chronic graft versus host disease (GVHD) within 4 weeks prior to enrollment
- •Donor lymphocyte infusions (DLI) permitted if ≥4 weeks prior to leukapheresis
- •History of secondary CNS or meningeal involvement allowed if:
- •cannot be the only site of disease
- •absence of neurologic symptoms, such as: seizures, stroke-like deficits, altered mental status, aphasia, or psychosis
- •Adequate organ function at time of screening, including:
- •ALT or AST ≤5x ULN and total bilirubin ≤2 (or ≤3 if history of Gilbert's syndrome or leukemic infiltration of the liver)
- •Serum creatinine <2.0mg/100mL
- •SaO2 ≥92% on room air
- •Left ventricular ejection fraction (LVEF) ≥50% within 1 month of screening
- •ECOG performance status 0-1 or Lansky performance status ≥ 60 for patients < 16 years old
- •Prior CD19-targeted therapies (including CD19 CAR-T cell and CD19 bispecific T-cell engagers) are allowed including anti-CD19 CAR T therapy, as long as CD19 positivity is confirmed on most recent bone marrow, blood or tumor biopsy
排除标准
- •Concurrent active malignancy excluding: nonmelanoma skin cancer or localized solid tumor that has undergone definitive therapy and with low risk of recurrence, e.g., prostate, breast
- •Burkitt's leukemia or lymphoma or CML in lymphoid blast crisis
- •Radiologically detected or symptomatic CNS disease or CNS 3 disease (i.e., presence of ≥5/µL WBCs in CSF). Subjects with adequately treated CNS leukemia are eligible.
- •The following medications are excluded:
- •Steroids: Therapeutic doses of corticosteroids (greater than 10mg daily of prednisone or its equivalent) within 7 days of leukapheresis or 72 hours prior to CAR T cell infusion.
- •Chemotherapy: Systemic chemotherapy should be stopped one week prior to leukapheresis or starting CAR T cell infusion or lymphodepleting chemotherapy. Hydroxyurea for cytoreduction can be administered up to 72 hours before leukapheresis or CAR T cell infusion.
- •History of class III-IV New York Heart Association (NYHA) heart failure, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac condition within 6 months of screening
- •Patients with history of significant autoimmune disease and/or inflammatory condition affecting the CNS are ineligible
- •Systemic treatment for GVHD within 4 weeks prior to enrollment
- •Patients with known severe autoimmune disease (e.g., Crohn's, rheumatoid arthritis, or lupus) that in the investigator's opinion has high likelihood of requiring systemic immune suppressive medications
- •Patients with HIV infection
- •Patients with active hepatitis B infection (as manifested by either detectable hepatitis B virus DNA by PCR and/or positivity for hepatitis B surface antigen)
- •Patients with active hepatitis C infection (as manifested by detectable hepatitis C virus RNA by PCR)
- •Patients with uncontrolled systemic fungal, bacterial, viral or other infection including COVID-19 at time of leukapheresis or at time of CAR T cell infusion.
- •Other uncontrolled medical or psychological conditions as well as social or logistical issues that may interfere with compliance with the protocol, as determined by the investigator
- •Treatment with live, attenuated vaccine <4 weeks prior to leukapheresis
- •Pregnant or lactating/breastfeeding women
研究组 & 干预措施
Dose Level 1
Experimental
0.5x106 CAR-T cell/kg without lymphodepleting chemotherapy (LDC)
干预措施: 19-28z/IL-18 CAR T cells (Biological)
Dose Level 2
Experimental
0.5x106 cells/kg with lymphodepleting chemotherapy (LDC)
干预措施: 19-28z/IL-18 CAR T cells (Biological)
Dose Level 3
Experimental
1x106 cells/kg with lymphodepleting chemotherapy (LDC)
干预措施: 19-28z/IL-18 CAR T cells (Biological)
结局指标
主要结局
Toxicity as determined by CTCAE, version 5.0
时间窗: 4 weeks
The primary objective is to determine the safety of 19-28z/IL18 CAR T cells in patients with R/R ALL. Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
次要结局
未报告次要终点
研究者
研究点 (14)
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