A Phase 1/2 Study of T-cell Expressing a Novel CD19 Chimeric-Antigen Receptor (SHB-02-CD19) in Patients With CD19-expressing B-cell Malignancies

This is a phase I/II trial of SHB-02-CD19, T-cell expressing an anti-CD19 Chimeric-Antigen-Receptor (CAR) in patients with CD19 expressing B-cell malignancies. This trial is an open label, single-arm, for pediatric and adult patients with relapsed/refractory B-cell malignancies.

Study Overview

• Status: Not yet recruiting
• Conditions: B Cell Malignancies; Acute Lymphobkastic Leukemia; Non-Hodgekin Lymphoma (NHL-both Follicular & Diffuse Large Cell)
• Intervention / Treatment: Drug: SHB-02-CD19 (anti CD19 CAR-T cells)

Detailed 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.

In this trial, patient will be treated with SHB-02-CD19, a novel CAR-T treatment manufactured by the Advanced Biotherapy Center (ABC) at the Sheba Medical Center, that uses a different construct than the commercial CAR-T products. The SHB-02-CD19 has a unique mutation in the CAR signaling domain, which is expected to improve efficacy while reducing toxicities, meaning this product is expected to have better clinical results at lower cell doses compared to the conventional CD19 CAR-T therapies.

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 encodes a CAR which recognizes the CD19 antigen. Patients will receive lymphodepleting chemotherapy followed by a single dose of SHB-02-CD19, after which they will be monitored and undergo various research assessments (including blood 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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sivan Yakobi; Phone Number: 972-03-5309046; Email: sivan.yakobi@sheba.health.gov.il

Study Locations

• Israel
  • Ramat Gan, Israel
    • Sheba Medical Center
    • Contact: Sivan Yakobi; Phone Number: 972-03-5309046; Email: sivan.yakobi@sheba.health.gov.il
    • Principal Investigator: Prof. Elad Jacoby, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient must have a CD19-expressing hematologic malignancy, relapsed or refractory after receiving at least 2 lines of standard therapy and not eligible for current commercial CD19 CAR T cells per Israeli MOH health basket:

  1. Relapse following standard relapse protocol (2nd relapse)
  2. Primary refractory, i.e. failed to achieve morphologic remission after 2 lines of induction chemotherapy.
  3. Patients who have histologically confirmed large B-cell lymphoma, according to the World Health Organization 2016 classification criteria, that are refractory to first-line treatment or that have relapsed from complete remission no more than 12 months after the completion of first-line chemo-immunotherapy including an anti-CD20 monoclonal antibody and anthracycline-containing regimen.
  4. Very high risk 1st relapse of ALL, defined as (a) relapse within 18 months of initial diagnosis; (b) relapse with the following cytogenetic abnormalities: KMT2a-R, TCF3::HLF, TCF3::PBX1, TP53-alterations.
• Age 1-80 years
• For ALL, CD19 expression shown by flow cytometry or immunohistochemistry on at least 70% of leukemic blasts.
• 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
• No prior CD19 CAR T cell administered

• Prior therapy:

  1. Patients should be off steroids for at least 2 weeks prior to apheresis
  2. Patients should be off systemic anti-neoplastic treatment for 2 weeks prior to apheresis, with the exception of intrathecal chemotherapy. Patients who received prior clofarabine and fludarabine should have a wash out period of 3 months prior to apheresis.
  3. Patients should have recovered from all toxicities attributed to prior therapy. Cytopenias that are considered disease related rather than therapy related are exempt from this exclusion.
  4. Radiation therapy should be completed at least 3 weeks prior to apheresis.

Exclusion Criteria:

• Hyperleukocytosis (WBC>50,000) or rapidly progressive disease that in the judgment of the PI can compromise the ability of the patient to complete the study
• Pregnant or breast-feeding females
• Hepatic dysfunction, defined as bilirubin > x2 upper normal limit (except when explained by hemolysis or Gilbert) or SGOT > x2.5 upper normal limit.
• Active HIV infection, HBV or HCV infection which is identified by positive PCR of viral sequences. Patients who are positive for HCV Abs, HBsAg and/or positive to HBcAbs total, will be evaluated by PCR of viral sequences. If PCR is positive, the patient will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single arm, open label, dose escalation: SHB-02-CD19 (anti CD19 CAR-T); anti CD19 CAR-T cells

Drug: SHB-02-CD19 (anti CD19 CAR-T cells); Phase 1 of this study includes a dose escalation plan of SHB-02-CD19. Treatment will start at dose level 1. According to safety assessments, dose will increase to next dose level. Dose level 1: 0.25x10^6 CAR+ T cells per kilogram Dose level 2: 0.5x10^6 CAR+ T cells per kilogram Dose level 3: 1x10^6 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Evaluation: Treatment Related Toxicities	An evaluation of safety of the use of SHB-02-CD19 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 SHB-02-CD19 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 and minimal-residual disease (MRD) in the 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 SHB-02-CD19. 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.

Collaborators and Investigators

• Sponsor: Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: March 25, 2026
• First Submitted That Met QC Criteria: March 25, 2026
• First Posted (Actual): March 31, 2026

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: DLBCL; CAR-T; NHL; ALL; CD-19
• Other Study ID Numbers: SHB-02-CD19; 2757-25-SMC (Other Identifier: Sheba Helsinki committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only IPD used in the results publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No