NCT02650414进行中（未招募）1 期
Pilot Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells in Pediatric Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS)
研究概览
简要总结
This is a pilot study to determine the feasibility and safety of a single dose of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCR-ζ and 4-1BB signaling domains (CART22/CART22-65s cells) in pediatric and young adult subjects with relapsed or refractory B cell acute lymphoblastic leukemia.
详细描述
This is a single center, single arm, dual-cohort, open-label pilot study to determine the feasibility and safety of a single dose (administered as split fractions) of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-
1BB) co-stimulatory domains (referred to as "CART22" and "CART22-65s" cells) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Cohort assignment will be dependent on the date of consent and confirmation of eligibility by a physician-investigator as follows:
- Cohort 1: was closed to additional recruitment as of Protocol Version 8. All subjects who received CART22 cells will be retrospectively assigned to Cohort 1.
- Cohort 2: was opened as of Protocol Version 8. All subjects assigned to Cohort 2 will receive CART22-65s cells given over 3 days.
- Cohort 3: will open as of Protocol V12, with subjects enrolled sequentially after all infusion slots in Cohort 2 are filled. All subjects assigned to Cohort 3 will also receive CART22-65s cells, however the product will be administered over 2 days.
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
- 1 Year 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form must be obtained prior to any study procedure.
- •Relapsed or refractory B-cell ALL:
- •2nd or greater relapse OR
- •Any marrow or extramedullary relapse after allogeneic HSCT and ≥ 6 months from SCT at infusion OR
- •Any marrow relapse after CAR-modified T cell therapy OR
- •Refractory disease defined as having not achieved a CR after > 2 chemotherapy regimens OR
- •Patients with Ph+ ALL are eligible if they are intolerant to or have failed tyrosine kinase inhibitor therapy OR
- •Ineligible for allogeneic SCT because of:
- •i. Comorbid disease ii. Other contraindications to allogeneic SCT conditioning regimen iii. Lack of suitable donor iv. Prior SCT v. Declines allogeneic SCT as a therapeutic option after documented discussion, with expected outcomes, about the role of SCT with a BMT physician not part of the study team g. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion, must meet criteria in Section 5.2)
- •Documentation of CD22 tumor expression in bone marrow, other tumor biopsy, CSF or peripheral blood by flow cytometry (or a recent marrow in the case of refractory disease). If the patient has received CD22-directed therapy (i.e., inotuzumab), then the marrow or other sample should be obtained after this therapy to show CD22 expression.
- •Adequate organ function defined as:
- •A serum creatinine based on age/gender as follows:
- •Maximum Serum Creatinine (mg/dL) Age 1 to < 2 years Male 0.6 Female 0.6 Age 2 to < 6 years Male 0.8 Female 0.8 Age 6 to < 10 years Male 1.0 Female 1.0 Age 10 to < 13 years Male 1.2 Female 1.2 Age 13 to < 16 years Male 1.5 Female 1.4 Age ≥ 16 years Male 1.7 Female 1.4
- •Adequate liver function
- •i. ALT < 500 U/L ii. Bilirubin <3x upper limit of normal iii. ALT and/or bilirubin that exceed these ranges is acceptable if, in the opinion of the investigator (or by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver c. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen > 92% on room air; DLCO > 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator d. Left Ventricle Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA; in cases where quantitative assessment of LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice.
- •Evidence of disease by standard morphologic or by MRD criteria. If the results of a historical biopsy (obtained at the time of the patient's most recent relapse) are available, this does not need to be repeated at screening.
- •Age 1-29 years.
- •Adequate performance status (Lansky or Karnofsky score ≥50).
- •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-versus-host disease (GVHD) requiring systemic therapy.
- •Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary.
- •CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
- •Pregnant or nursing (lactating) women.
- •Receipt of a prior investigational study agent within 4 weeks prior to screening visit. *Note - patients who have received anti-CD19 CART cells (e.g., CART19/CTL019) on an investigational study where cell infusion occurred greater than 4 weeks before the screening visit are NOT excluded.
研究组 & 干预措施
Pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia
Experimental
干预措施: Cohort 1 (Biological)
Pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia
Experimental
干预措施: Cohorts 2 (Biological)
Pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia
Experimental
干预措施: Cohort 3 (Biological)
结局指标
主要结局
Frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS)
时间窗: From date of dosing ( day 1 ) up 15 years
grade 3 and higher toxicity rate (toxicity possibly attributed to CART22)
The frequency and severity of adverse events.
时间窗: From date of dosing ( day 1 ) up 15 years
Grade 3 and higher toxicity rate (toxicity possibly attributed to CART22 or CART22-65s) that is unmanageable, unexpected and unrelated to chemotherapy.
次要结局
- Percentage of manufacturing products that do not meet release criteria.(3 months)
- Overall Complete Remission Rate (ORR) at Day 28.(4 months)
- Evaluate disease status at Month 6.(9 months)
- Describe response in terms of minimal residual disease (MRD).(1 year)
- Incidence of any grade II-IV aGVHD(15 year)
- Incidence any chronic GVHD.(15 year)
- Incidence any extensive, limited cGVHD.(15 year)
- Evaluate overall response rate (CR/CRi by or at Month 6) at Month 6.(9 months)
- Overall survival (OS)(15 years)
- Duration of remission (DOR)(15 Years)
- Number of subjects with relapse free survival (RFS)(15 years)
- Number of subjects with event free survival (EFS).(15 years)
- Describe cause of death (COD) when appropriate(15 years)
- Incidence of any acute GVHD(15 year)
- Overall survival (OS)(From date of dosing ( day 1 ) up 15 years)
研究者
研究点 (1)
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