CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Patient must have a CD22-expressing hematologic malignancy, relapsed or refractory after receiving at least 2 lines of standard therapy including CD19-directed therapy (For CD19 positive disease):
* Relapse following standard relapse protocol (2nd relapse), including CD19 CART.
* Primary refractory, i.e. failed to achieve morphologic remission after 2 lines of induction chemotherapy.
* Age 1-80 years
* CD22 expression shown by flow cytometry on at least 70% of leukemic blasts / lymphoma cells
* Adequate CD3 count (above 120 CD3+ cells per microliter blood)
* Clinical performance status: Patients \> 10 years of age: Karnofsky ≥ 50%; Patients ≤ 10 years of age: Lansky scale ≥ 50%. Exception for neurologic symptoms (e.g. paralysis) that are explained by the malignancy.
* Females of child-bearing potential must have a negative pregnancy test
* Cardiac function: LV ejection fraction \>45% or shortening fraction \>28%
* At least 60 days after autologous or allogeneic BMT
* At least 30 days after prior CAR therapy in absence of response

主要终点：Safety Evaluation: Treatment Related Toxicities · An evaluation of safety of the use of autologous anti-CD22 CAR T cells (SHB-04-CD22) manufactured at the Sheba Medical Center, in patients with relapsed/refractory B-cell malignancies. Safety will be determined by evaluation of participants with treatment-related adverse events, as assessed by CTCAE 5.0. · From enrollment to 3 months post treatment.；Efficacy Evaluation · An evaluation of the feasibility and efficacy of administering anti-CD22-CAR T cells (SHB-04-CD22) in patients with B-cell malignancies at the Sheba Medical Center. Efficacy will be determined by an evaluation of disease response in participants post treatment. Disease response will be assessed by blasts percentage in bone marrow for ALL patients and by PET-CT scan based on the Lugano classification for NHL patients. · 1 month to 1 year post treatment.；Minimal toxic dose evaluation · An evaluation of the minimal toxic dose of CD22 CAR-T cells (SHB-04-CD22). This will be determined by evaluation of participants with treatment-related adverse events, as assessed by CTCAE 5.0, and according to different dose levels administered. · From first dose to end 3 months post treatment.

• Single arm, open label, dose escalation: Anti CD22 CAR-T (SHB-04-CD22) · EXPERIMENTAL · Phase 1 of this study includes a dose escalation plan of anti CD22 CAR-T (SHB-04-CD22). Treatment will start at dose level 1. According to safety assessments, dose will increase to next dose level. Dose level 1: 3x10\^5 CAR+ T cells per kilogram Dose level 2: 1x10\^6 CAR+ T cells per kilogram Dose level 3: 3x10\^6 CAR+ T cells per kilogram Phase 2 of this study will be a dose expansion phase of the dose recommended based on safety and expected efficacy.

This is a phase I/II trial of T-cell expressing an anti-CD22 Chimeric-Antigen-Receptor (CAR) in patients with CD22 expressing B-cell malignancies. This trial is an open label, single-arm, for pediatric and adult patients with relapsed/refractory B-cell malignancies.