Clinical Study on the Efficacy and Safety of CD19 CAR-T Cell Infusion as Consolidation Therapy in Adolescent and Adult Patients With Acute B-Lymphoblastic Leukemia Who Are Ineligible for Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Leukemia-Free Survival(LFS)
研究概览
简要总结
This clinical study investigates a novel treatment option for adolescents and adults with acute B-lymphoblastic leukemia (B-ALL). While allogeneic hematopoietic stem cell transplantation (HSCT) is a standard therapy for leukemia, some patients are ineligible due to factors such as age, underlying medical conditions, or the absence of a suitable donor. For these individuals, CD19 CAR-T cell therapy is being evaluated as a potential consolidation therapy.
详细描述
This is an open-label, single-arm, prospective clinical study designed to evaluate the clinical effectiveness and safety of CD19-directed chimeric antigen receptor T (CAR-T) cell therapy as a consolidation treatment in adolescent and adult patients with acute B-ALL who are ineligible for allogeneic HSCT. The study is planned to be conducted over a period of three years, enrolling a total of 30 participants.The primary objective of this study is to assess the clinical effectiveness of CD19 CAR-T cell therapy as a consolidation therapy in achieving remission and improving survival outcomes in the specified patient population. Specifically, the study aims to:
Evaluate the efficacy of CD19 CAR-T cell therapy in achieving complete remission (CR) or minimal residual disease-negative (MRD-) status in patients with B-ALL.
Assess the safety and tolerability of the treatment, with a focus on key adverse events.
Eligible participants will receive CD19 CAR-T cell infusion following a standard lymphodepleting chemotherapy regimen. After infusion, patients will be closely monitored for both short-term and long-term outcomes. Safety Considerations:
Patients will be closely monitored for treatment-related toxicities. Early intervention strategies for CRS and neurotoxicity will be implemented as per established management guidelines. Supportive care, including corticosteroids and anti-cytokine therapies, will be available for severe toxicities.
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
- 14 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject has voluntarily agreed to participate, signed the informed consent form, and is willing and able to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.
- •The subject has been clinically diagnosed with newly diagnosed or refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL), including Burkitt lymphoma leukemia and blast-phase chronic myeloid leukemia, and has achieved complete remission (defined as <5% bone marrow blasts, no peripheral blood blasts, and no extramedullary leukemia) after chemotherapy or immunotherapy, but is either ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT), lacks a suitable donor, or declines transplantation.
- •Aged between 14 and 80 years (inclusive), male or female.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •At the time of screening, leukemia cells in the bone marrow or peripheral blood must be confirmed as CD19-positive by flow cytometry at initial or relapse diagnosis.
- •An expected survival of more than three months from the date of signing the informed consent form.
- •Satisfactory liver, kidney, cardiac, and pulmonary function, defined as:
- •Creatinine ≤2× upper limit of normal (ULN);
- •Left ventricular ejection fraction (LVEF) ≥50%;
- •Blood oxygen saturation >92%;
- •Total bilirubin ≤2× ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× ULN.
- •Adequate venous access for cell collection and meeting the following hematologic criteria:
- •Hemoglobin ≥80 g/L Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L Platelet count ≥75 × 10⁹/L If the above criteria are not met, the investigator may determine eligibility for mononuclear cell collection.
- •Female subjects of childbearing potential must have a negative serum pregnancy test (women who have undergone surgical sterilization or have been postmenopausal for at least two years are considered non-fertile). Male and female subjects of reproductive potential must agree to use contraception during the study.
排除标准
- •Presence of mixed-lineage leukemia or biphenotypic leukemia.
- •Prior treatment with CAR-T cell therapy before screening or conditioning.
- •Patients with bone marrow failure syndromes associated with genetic disorders, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndromes.
- •Any of the following viral infections:
- •Hepatitis B virus (HBV) DNA detectable above the lower limit of quantification. Positive hepatitis C virus antibody (HCV-Ab). Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA detectable above the lower limit of quantification.
- •Positive human immunodeficiency virus (HIV) antibody test.
- •History of or current malignancy within the past five years (excluding patients with a low risk of recurrence after curative treatment and more than five years of follow-up, as determined by the investigator).
- •Any of the following cardiac conditions:
- •New York Heart Association (NYHA) Class III or IV congestive heart failure. Severe arrhythmia requiring treatment or clinically significant conduction abnormalities on ECG, including QTc interval ≥480 ms (QTcB = QT/√RR).
- •Uncontrolled hypertension despite standard treatment (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg) or pulmonary hypertension.
- •Unstable angina. Myocardial infarction, coronary artery bypass grafting, or stent placement within six months before cell infusion.
- •Clinically significant valvular heart disease. Other cardiac diseases deemed inappropriate for study participation by the investigator.
- •Uncontrolled epilepsy, a history of cerebrovascular ischemia/hemorrhage, cerebellar disease, or other active central nervous system (CNS) disorders.
- •Clinically significant pericardial or pleural effusion at screening.
- •History of deep vein thrombosis or pulmonary embolism within six months before screening.
- •Known hypersensitivity to any component of the study treatment.
- •Live vaccine administration within six weeks before screening.
- •Severe, uncontrolled, active infection at screening.
- •Participation in other interventional clinical trials and receipt of an investigational agent, including:
- •An unapproved investigational drug within three months before cell infusion. A marketed drug within fewer than five half-lives before cell infusion.
- •Any other conditions deemed unsuitable for study participation by the investigator.
- •Physical or cognitive conditions that impair the ability to provide informed consent or comply with study procedures, or unwillingness or inability to adhere to study requirements.
研究组 & 干预措施
Consolidation therapy with CAR-T cells was performed after induced remission
For autologous intravenous infusion only, the recommended dose is 0.5×108 CAR-T live cells, and the dose range is 0.25~0.5×108 CAR-T live cells (±20%, i.e. 0.2-0.6×108 CAR-T live cells)
干预措施: CD19 CAR-T cells injection (Drug)
结局指标
主要结局
Leukemia-Free Survival(LFS)
时间窗: From Chimeric Antigen Receptor T-Cell infusion to relapse or death, assessed up to 12 months
Relapse defined by ≥ BM blasts(ELN 2022)
次要结局
未报告次要终点