A Phase 1/2 Study of T-cell Expressing an Anti-CD22 Chimeric-Antigen Receptor (SHB-04-CD22) in Patients With CD22-expressing B-cell Malignancies

B-cell precursor Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, and an adult malignancy with poor prognosis. B-cell non-Hodgkin lymphoma (NHL) and common lymphocytic leukemia (CLL) arise from mature B-cells, and are more commonly seen in the adult and elderly population. In the recent decade, advances in immunotherapy targeting cell surface markers, using antibodies, antibody-drug conjugates, bispecific antibodies or CAR-T cells, have improved the outcome of patients with relapsed and refractory B-cell malignancies. CAR-T cell products targeting CD19, a common B-cell antigen, are approved for B-cell malignancies. Treatment with CD19 CAR-T cells was FDA approved for pediatric ALL, adult ALL, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, mantle-cell lymphoma (MCL) and primary mediastinal B-cell lymphoma (PMBCL). Still, most patients with B-cell malignancies treated nowadays with commercial CD19 CAR T-cells relapse. To address this, alternative immunotherapy targets have been proposed. CD22 is an additional co-receptor on B-cells, commonly expressed in B-cell malignancies such as ALL, and has been most studied in this context. Autologous T cells will be harvested from patients with B-cell malignancies and then activated and transduced with a retrovirus containing a chimeric-antigen receptor (CAR), manufactured by the Advanced Biotherapy Center (ABC) at the Sheba Medical Center. Patients will undergo a one-time cell collection via apheresis, after which the cells will be sent to the laboratory for activation and introduction of a gene that recognizes the CD22 antigen. Patients will receive lymphodepleting chemotherapy followed by a single dose of CD22 CAR-T cells (SHB-04-CD22), after which they will be monitored and undergo various research assessments (including blood tests, genetic tests, and assessments of the disease status). Patients will be closely monitored for approximately 3 months after treatment to assess response and safety of the treatment. Long-term survival monitoring will take place once a year for 15 years.

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