CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Male and female subjects age ≥ 1 and ≤ 30 years
* First 2 enrolled subjects: age ≥ 18 and ≤ 30 years
* Disease requirements:

  * Phase 1: Evidence of refractory or recurrent CD19+ leukemia or lymphoma following previous CAR T cell immunotherapy
  * Phase 2: Evidence of refractory or recurrent CD19+ leukemia or lymphoma
* Able to tolerate apheresis, or has sufficient existing apheresis product or T cells for manufacturing investigational product
* Life expectancy ≥ 8 weeks
* Lansky or Karnofsky, as applicable, score ≥ 50
* Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy, if the subject does not have a previously obtained apheresis product that is acceptable and available for manufacturing of CAR T cells
* ≥ 7 days post last chemotherapy and biologic therapy, with the exception of intrathecal chemotherapy and maintenance chemotherapy
* No prior virotherapy
* ≥ 7 days post last corticosteroid therapy
* ≥ 3 days post Tyrosine Kinase Inhibitor (TKI) use
* ≥ 1 day post hydroxyurea
* 30 days post most recent CAR T cell infusion
* Adequate organ function
* Adequate laboratory values, including absolute lymphocyte count ≥ 100 cells/uL
* Subjects of childbearing or child-fathering potential must agree to use highly effective contraception from consent through 12 months following infusion of investigational product on trial
* Subject and/or legally authorized representative has signed the informed consent form for this study

Exclusion Criteria:

* Presence of active malignancy other than disease under study
* History of symptomatic CNS pathology or ongoing symptomatic CNS pathology
* CNS involvement of leukemia or lymphoma that is symptomatic and in the opinion of the investigator, cannot be controlled during the interval between enrollment and CAR T cell infusion
* Presence of active GVHD, or receiving immunosuppressive therapy for treatment or prevention of GVHD within 4 weeks prior to enrollment
* Presence of active severe infection
* Presence of primary immunodeficiency syndrome
* Subject has received prior virotherapy
* Pregnant or breastfeeding
* Subject and/or legally authorized representative unwilling to provide consent/assent for participation in the 15-year follow up period, required if CAR T cell therapy is administered
* Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol

主要终点：The adverse events associated with CAR T cell product infusions will be assessed · The type, frequency, severity, and duration of adverse events will be summarized · 30 days；The leukemia response to SCRI-huCAR19 in subjects with relapsed or refractory CD19+ leukemia will be assessed · Response will be defined by standard bone marrow assessment and standard response criteria · 63 days

• SCRI-huCAR19v2 · EXPERIMENTAL · Patients will receive SCRI-huCAR19v2 in either Phase 1 or Phase II
• SCRI-huCAR19v1 - [CLOSED] · EXPERIMENTAL · Patients will receive SCRI-huCAR19v1 in either Phase 1 or Phase II. As of 02/13/2020 this study cohort is permanently closed.

Patients with relapsed or refractory leukemia or lymphoma are often refractory to further chemotherapy. In this study, the investigators will attempt to use T cells obtained directly from the patient, which can be genetically engineered to express a fully human chimeric antigen receptor (CAR). The CAR used in this study can recognize CD19, a protein expressed on the surface of leukemia and lymphoma cells. The fully human CAR used in this study may help protect against rejection of the CAR T cells, which in turn could lead to lasting protection against return of the leukemia or lymphoma. The phase 1 part of this study will determine the safety of these CAR T cells, and the phase 2 part of the study will determine how effective this CAR T cell therapy is. Both patients who have never had prior CAR T cell therapy and those who have had prior CAR T cell therapy may be eligible to participate in this study.