Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD33 Linked to TCRζ And 4-1BB Signaling Domains In Combination With CD33KO-HSPC In Subjects With Refractory Or Relapsed Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Occurrence of dose-limiting toxicities related to CD33KO-HSPC
研究概览
简要总结
The purpose of this study is to provide a new type of treatment for AML. This treatment combines a new type of stem cell transplant along with treatment using chimeric antigen receptor (CAR) T cells that have been engineered to recognize and attack your AML cells.
The first treatment is a modified stem cell transplant, using blood-forming stem cells donated from a healthy donor. From the same donor, we will also make CAR T-cells, which are leukemia fighting cells, which will be given to the patient via an infusion into the vein after the transplanted stem cells have started to grow healthy blood cells. The modification of the stem cell transplant means that the healthy bone marrow cells will be "invisible" to the CAR T-cells that are trying to kill the leukemia cells.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female 18 years of age or older
- •Subjects with AML unlikely to be cured with currently available therapies
- •AML that has not achieved a complete remission or morphologic leukemia free state by ELN criteria; partial remission or refractory disease (including primary refractory) are eligible; OR:
- •AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplantation). Note: morphologic relapse is not required; persistent/recurrent disease-associated molecular, phenotypic or cytogenetic abnormalities (measurable residual disease, MRD) at any time after allogeneic HCT is eligible; OR:
- •Subjects with relapsed disease after prior transplant must be off systemic immunosuppression for at least 1 month at the time of enrollment.
- •Subjects must have a suitable stem cell donor.
- •Satisfactory organ function
- •Creatinine clearance > 40 ml/min
- •ALT/AST must be ≤ 5x upper limit of normal unless related to disease and < 20 x upper limit of normal if related to disease
- •Direct bilirubin < 2.0 mg/dl, unless subject has Gilbert's syndrome (≤ 3.0 mg/dL)
- •Left ventricular ejection fraction ≥ 40% as confirmed by echocardiogram or MUGA
- •DLCO > 45% predicted
- •ECOG performance status 0-1
- •Written informed consent is given
- •Subjects of reproductive potential must agree to use acceptable birth control methods
排除标准
- •Pregnant or lactating (nursing) women
- •Active hepatitis B or hepatitis C or HIV infection
- •Concurrent use of systemic steroids or immunosuppressant medications
- •Any uncontrolled active medical disorder that would preclude participation as outlined
- •Subjects with signs or symptoms indicative of CNS involvement.
- •Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- •Class III/IV cardiovascular disability according to New York Heart Association Classification
- •Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the screening/enrollment visit.
研究组 & 干预措施
CD33KO-HSPC followed by CART33
All subjects will receive CD33KO-HSPC, followed by 1-3 CART-33 infusions
干预措施: CD33KO-HSPC; CART33 (Biological)
结局指标
主要结局
Occurrence of dose-limiting toxicities related to CD33KO-HSPC
时间窗: 3 months
Safety of alloHSCT: occurrence of dose-limiting toxicities related to CD33KO-HSPC
Manufacturing feasibility
时间窗: 1 month
Proportion of subjects whose Product 1 (CD33KO-HSPC) meets release criteria.
Occurrence of dose-limiting toxicities related to CART-33
时间窗: 6 months
Safety of CART-33: occurrence of dose-limiting toxicities related to CART-33
次要结局
- Efficacy of CD33KO-HSPC(1 month)
- Efficacy of at least 1 dose of CART-33(6 months)
- Overall Survival (OS)(6 months, 12 months)
- Duration of Response (DOR)(15 years)
- Progression free survival (PFS)(6 months, 12 months)