Use of Autologous Anti-CD22 CAR T Cells (CART22-65s) Co-administered With Humanized Anti-CD19 CAR T Cells (huCART19) in Children and Young Adults With Relapsed or Refractory B-ALL
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 93
- 试验地点
- 2
- 主要终点
- Safety of CART22-65s and huCART19 co-administration
研究概览
简要总结
This study will evaluate the safety and efficacy of administering two CAR T cell products, huCART19 and CART22-65s, in children with advanced B cell Acute Lymphoblastic Leukemia (B-ALL).
详细描述
CD19-targeted CAR T cell therapy has transformed the treatment landscape for children and young adults with chemo-refractory or relapsed B cell Acute Lymphoblastic Leukemia (B-ALL). Despite remarkable initial response rates, approximately 50% of pediatric patients experience a subsequent disease relapse. The prognosis for these patients is dismal with a median survival of less than one year from the time of post-CART19 relapse. The primary mechanisms contributing to CART19 failure include CD19-antigen escape and loss of CAR T cell surveillance due to short CART persistence. This study aims to counter each driver of relapse by co-administering two next-generation CAR T cell products: an anti-CD22 CART (CART22-65s), designed to overcome CD19-antigen escape; and a humanized anti-CD19 CART (huCART19), designed to overcome immune-mediated rejection of murine CART19.
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
- — 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form
- •Patients with documented CD19+ and/or CD22+ ALL/LLy:
- •Cohort A: Patients with relapsed or refractory ALL/LLy:
- •Cohort B: Patients with poor response to prior B cell directed engineered cell therapy
- •Patients with prior or current history of Central Nervous System 3 disease will be eligible if Central Nervous System disease is responsive to therapy
- •Documentation of CD19 and/or CD22 tumor expression in bone marrow, peripheral blood, Cerebrospinal fluid, or tumor tissue by flow cytometry at the time of last detectable disease. If the patient has experienced a relapse after CD19-directed and/or CD22-directed therapy, flow cytometry should be evaluated after this therapy to demonstrate CD19 and/or CD22 expression.
- •Age 0-29 years
- •Adequate organ function
- •Adequate performance status defined as Lanksy or Karnofsky performance score ≥
- •Subjects of reproductive potential must agree to use acceptable birth control methods.
排除标准
- •Active hepatitis B or active hepatitis C
- •HIV infection
- •Active acute or chronic Graft Vs. Host Disease requiring systemic therapy
- •Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- •Central nervous system disease that is progressive on therapy, or with Central nervous system parenchymal lesions that might increase the risk of central nervous system toxicity.
- •Pregnant or nursing (lactating) women
- •Uncontrolled active infection
研究组 & 干预措施
Dose Finding Arm
Phase 1 will evaluate the safety of co-administration of CART22-65s with huCART19 in patients who experienced a disease relapse after prior CAR T cell therapy. There is no planned dose escalation but a dose-deescalation will be made based on the incidence of Dose Limiting Toxicities
干预措施: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s) (Biological)
Dose Finding Arm
Phase 1 will evaluate the safety of co-administration of CART22-65s with huCART19 in patients who experienced a disease relapse after prior CAR T cell therapy. There is no planned dose escalation but a dose-deescalation will be made based on the incidence of Dose Limiting Toxicities
干预措施: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19) (Biological)
Expansion Arm
If at least one dose level of phase 1 is determined to be safe, the phase 2 dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of CART 22-65s and huCART19 cells that were determined to be safe. 2 cohorts are planned: Cohort A (relapsed/refractory, CAR T cell naïve) & Cohort B (prior treatment with a prior CAR T cell product).
干预措施: Autologous, humanized anti-CD22 CAR T cell therapy (CART22-65s) (Biological)
Expansion Arm
If at least one dose level of phase 1 is determined to be safe, the phase 2 dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of CART 22-65s and huCART19 cells that were determined to be safe. 2 cohorts are planned: Cohort A (relapsed/refractory, CAR T cell naïve) & Cohort B (prior treatment with a prior CAR T cell product).
干预措施: Autologous, humanized anti-CD19 CAR T cell therapy (huCART19) (Biological)
结局指标
主要结局
Safety of CART22-65s and huCART19 co-administration
时间窗: 1 year
The safety of the administering CART22-65s and huCART19 will be measured by the monitoring the frequency and severity of adverse events in patients with advanced or refractory B-Cell Acute Lymphoblastic Leukemia or B Cell Lymphoblastic Lymphoma (B-LLy), including those previously treated with cell therapy.
Efficacy of CART22-65s and huCART19 co-administration
时间窗: 1 year
The efficacy of CART22-65s and huCART19 co-administration will be measured by the evaluating the overall response rate in patients with advanced or refractory B cell hematologic malignancies, including those previously treated with cell therapy.
次要结局
- Relapse Free Survival(1 year)
- Overall Survival(1 year)
- Anti-tumor response due to CART22-65s and huCART19 co-administration(Day 28)
- Bioreactivity of CART22-65s and huCART19 when co-administered(1 year)
- Manufacturing Feasibility(5 years)
- Event Free Survival(1 year)
- CAR T Cell Therapy Persistence(1 year)
研究者
Stephan Grupp MD PhD
Chief, Cell Therapy and Transplant Section Director, Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy Medical Director, Cell and Gene Therapy Lab
Children's Hospital of Philadelphia