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

Sheba Medical Center

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: B Cell Malignancies

Treatments: Other: CD22 CAR-T cells

Study type: Interventional

Funder types: Other

Identifiers

NCT07135466

SHB-04-CD22

2289-25-SMC (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 1 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Single arm, open label, dose escalation: Anti CD22 CAR-T (SHB-04-CD22)

Experimental group

Description:

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.

Treatment:

Other: CD22 CAR-T cells