NCT03620058进行中（未招募）1 期
Phase 1 Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells (CART22-65s) Alone and When Co-administered With Humanized Anti-CD19 Chimeric Antigen Receptor Redirected T Cells (huCART19) In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Assess the safety of combination CART22-65s and huCART19 in relapsed/refractory ALL Subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
研究概览
简要总结
This is a single center, open-label, phase 1 study to determine the safety and feasibility of infusing CART22-65s with or without huCART19 after administration of lymphodepleting chemotherapy in adult patients with relapsed or refractory B-ALL.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with relapsed or refractory B cell ALL:
- •a. Patients with 2nd or greater relapse or refractory to 1st salvage as defined by: i. Recurrent disease in the bone marrow identified morphologically, by immunohistochemistry or by Flow cytometry.
- •ii. Patients with extramedullary relapse only (no bone marrow involvement) will be eligible if disease response can be assessed radiographically b. Patients with refractory disease as defined by: i. Failure to achieve remission (<5% bone marrow blasts) after 2 cycles of induction chemotherapy ii. Patients that achieve remission but remain MRD+ after ≥2 cycles of induction chemotherapy.
- •c. Patients with Ph+ ALL are eligible provided they are intolerant to or have failed tyrosine kinase inhibitor therapy.
- •d. Patients with prior or current history of CNS3 disease* will be eligible only if CNS disease is responsive to therapy.
- •i. *CNS disease definitions:
- •CNS1 - no blasts seen on cytocentrifuge (CNS negative);
- •CNS2 - total nucleated cell count <5x106/L, but blasts seen on cytocentrifuge;
- •CNS3 - total nucleated cell count 5x106/L with blasts on cytocentrifuge and/or signs of CNS leukemia (i.e. cranial nerve palsy).
- •2. For Cohort 1: Documentation of CD22 expression on malignant cells at relapse. For Cohort 2: Documentation of CD22 and/or CD19
- •3. Adequate vital organ function defined as:
- •Creatinine ≤ 1.6 mg/dl
- •ALT/AST ≤ 3x upper limit of normal range
- •Total or Direct bilirubin ≤ 2.0 mg/dl. If Total bilirubin is ≤2.0, Direct bilirubin does not need to be assessed.
- •Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
- •4. Male or female age ≥ 18 years.
- •5. ECOG Performance Status that is either 0 or
- •6. No contraindications for leukapheresis.
- •7. Subjects of reproductive potential must agree to use acceptable birth control methods.
排除标准
- •1. Active hepatitis B or active hepatitis C.
- •2. HIV Infection.
- •3. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- •4. Subjects with clinically apparent arrhythmia or arrhythmias who are not stable on medical management within two weeks of eligibility confirmation by physician-investigator.
- •5. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
- •6. Planned concurrent treatment with systemic steroids or immunosuppressant medications. Patients may be on a stable low dose of steroids (<10mg equivalent of prednisone) for chronic respiratory conditions or adrenal insufficiency. For additional details regarding use of steroid and immunosuppressant medications.
- •7. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
- •8. Pregnant or nursing (lactating) women.
- •10. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
研究组 & 干预措施
CART22-65s monotherapy
Experimental
干预措施: CART22-65s cells (Biological)
CART22-65s in combination with huCART19
Experimental
干预措施: CART22-65s cells (Biological)
CART22-65s in combination with huCART19
Experimental
干预措施: huCART19 Cells (Biological)
结局指标
主要结局
Assess the safety of combination CART22-65s and huCART19 in relapsed/refractory ALL Subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
时间窗: 15 months
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
Assess the safety of CART22-65s in ALL subjects using the common terminology criteria of adverse events (CTCAE) v5.0.
时间窗: 15 months
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS).
次要结局
- Tumor response.(1 Year)
- Evaluate bioactivity of CAR T cells(1 Year)
- Determine antigen expression and normal B cell levels in response to CAR T cells(1 Year)
- CAR T cell kinetics(1 Year)
研究者
研究点 (1)
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