Phase I/II Study of Dual CD19-CD22 Chimeric Antigen Receptor (CAR) T Cells in Patients With Advanced CD19+ CD22+ Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Optimal chimeric antigen receptor (CAR) T cell dose level
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of modified immune cells called CD19-CD22 chimeric antigen receptor (CAR) T cells in treating patients with CD19 positive(+), CD22+ B-acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma that has come back (recurrent) or does not respond to treatment (refractory). T-cells are collected from the patient and genetic materials called "chimeric antigen receptors (CAR)" are transferred to the collected T-cells. The CAR T-cells are then infused back to the patient's body. Giving CD19- CD22 CAR T cells after chemotherapy may help to control the disease.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety of infusion with chimeric antigen receptor T cells targeting CD19 and CD22.
II. To find the recommended phase II dose for recurrent/refractory CD19+CD22+ B cell malignancies.
SECONDARY OBJECTIVES:
I. To describe the overall response rate and complete response rate of relapsed B cell malignancies treated with CAR-T cells targeting CD19 and CD22.
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
- 6 Months 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with relapsed/refractory B-acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), or non-Hodgkin's lymphoma (NHL) treated with at least two lines of therapy, and have persistent or progressed disease including positive minimal residual disease (MRD)
- •Patients may have received last cytotoxic chemotherapy at least 3 weeks prior to lymphodepleting chemotherapy
- •Patient may continue targeted therapy until 2 weeks before initiation of lymphodepleting chemotherapy with the exception of ibrutinib
- •Disease must be CD19 and/or CD22 positive by flow cytometry or immunohistochemistry
- •Karnofsky/Lansky performance scale > 70
- •Total bilirubin less than < 1.5 mg/dL except patients with Gilbert syndrome whose total bilirubin must be < 3.0mg/dL
- •Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 X upper limit of normal (ULN)
- •Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 5.0 ULN
- •Serum creatinine (as estimated by Cockcroft Gault) >= 60 cc/min
- •Cardiac ejection fraction >= 50% without evidence of pericardiac effusion as determined by echocardiogram (ECHO) or multigated acquisition scan (MUGA), no clinical significant electrocardiogram (ECG) findings
- •No clinical significant pleural effusion and baseline oxygen saturation >= 92%
- •Absolute lymphocyte count >= 100/ul
- •Be able to sign informed consent
- •All participants who are able to have children must practice effective birth control while on study. Acceptable forms of birth control for female patients include: birth control pills, patches, or injections, intrauterine device (IUD), diaphragm with spermicide, or condom with spermicide. Acceptable forms of birth control for male patients include condom with spermicide. If female participant becomes pregnant during the study, she will be taken off this study. If male participant fathers a child while on study, he must immediately notify his doctor
- •For patients with history of allogenic stem cell transplantation
- •Should not have active acute graft-versus-host disease (GVHD) grade >= 2
- •Should not be on immunosuppressants such as tacrolimus, sirolimus, cyclosporine, mycophenolates for a minimum of a month from CD19-CD22 CAR T cell infusion
- •Should not be on more than physiologic dose of systemic steroid for adrenal insufficiency (prednisone equivalent 5mg/day)
- •Transplantation should be more than 2 months from CD19-CD22 CAR T cell infusion
- •Other cell therapy including CAR T cells, donor lymphocyte infusion, virus specific T cells, natural killer (NK) cells, etc should have 6 weeks of wash-out period from the CD19-CD22 CAR T cell infusion
- •For patients with history of central nervous system (CNS) disease, CNS disease must be treated prior to enrollment
- •For patients with prior treatment history of cell therapy such as other CAR T cells or CAR NK cells or NK cells, cell therapy should have a 6 weeks of wash-out period from CD19-CD22 CAR T cell infusion
- •Be able to consent long-term follow-up protocol PA17-0483
排除标准
- •Positive beta-human chorionic gonadotropin (hCG) in female of child bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females
- •Known positive serology for human immunodeficiency virus (HIV)
- •Presence of active grade 3 or greater toxicity from the previous treatment
- •Presence of active fungal, bacterial, viral, or other infection requiring IV antibiotics for management
- •Presence of active neurologic disorders
- •Concomitant use of other investigational agents
- •Current use of corticosteroid more than physiological dose for adrenal insufficiency (prednisone equivalent at a dose higher than 10 mg/day)
- •Presence of active CNS disease
研究组 & 干预措施
Treatment (CD19-CD22 CAR T cells)
Patients receive standard of care cyclophosphamide IV over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells.
干预措施: Autologous CD19/CD22 Chimeric Antigen Receptor T-cells (Biological)
Treatment (CD19-CD22 CAR T cells)
Patients receive standard of care cyclophosphamide IV over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells.
干预措施: Cyclophosphamide (Drug)
Treatment (CD19-CD22 CAR T cells)
Patients receive standard of care cyclophosphamide IV over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Optimal chimeric antigen receptor (CAR) T cell dose level
时间窗: Up to 30 days
Dose-finding will be done using the sequentially adaptive phase I-II EffTox method.
Incidence of adverse events (adverse events)
时间窗: Up to 30 days
Toxicity is defined as a grade 3, 4, or 5 cytokine release syndrome, neurotoxicity, or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 with onset within 30 days of cell infusion. Adverse events that are considered disease-related (not suspected of relationship to CD19-CD22 -CAR T cells) will not be considered dose-limiting toxicities. Only those AEs that occur during the first 30 days after infusion, which are suspected to be related to conditioning lymphodepletion chemotherapy regimen and/or CD19 -CD22-CAR T cells (any component of the treatment regimen), and meet the following criteria, will be used in the definition of toxicity. Hematologic toxicities will not be considered in the definition of toxicity, as pancytopenia is a common toxicity with this regimen.
Efficacy in complete response (CR) or partial response
时间窗: Day 30 post cell infusion
Efficacy is defined as the patient being alive and in complete response (CR) or partial response (PR) at day 30 post cell infusion.
次要结局
- Overall survival(Up to 1 year post T-cell infusion)
- Progression-free survival(Up to 1 year post T-cell infusion)