B Cell MalignanciesPhase 1/2NCT07503353
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
A Phase 1/2 study testing SHB-02-CD19 (anti CD19 CAR-T cells) in people with B Cell Malignancies and Acute Lymphobkastic Leukemia, run by Sheba Medical Center at 1 site in Israel.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 year to 80 years
- Conditions the study is for
- B Cell Malignancies, Acute Lymphobkastic Leukemia, Non-Hodgekin Lymphoma (NHL-both Follicular & Diffuse Large Cell)
- What is being tested?
- SHB-02-CD19 (anti CD19 CAR-T cells)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2026to Jan 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- Relapse following standard relapse protocol (2nd relapse)
- Primary refractory, i.e. failed to achieve morphologic remission after 2 lines of induction chemotherapy.
- 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.
- 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
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- 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:
- Patients should be off steroids for at least 2 weeks prior to apheresis
- 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.
- 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.
- Radiation therapy should be completed at least 3 weeks prior to apheresis.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site
Sheba Medical Center
Ramat Gan
Sivan Yakobi, 972-03-5309046, sivan.yakobi@sheba.health.gov.il
Prof. Elad Jacoby, MD
About this study
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.
Read the 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.
- Conditions
- B Cell Malignancies, Acute Lymphobkastic Leukemia, Non-Hodgekin Lymphoma (NHL-both Follicular & Diffuse Large Cell)
- Being tested
- SHB-02-CD19 (anti CD19 CAR-T cells)
- Keywords
- ALL, DLBCL, NHL, CAR-T, CD-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHB-02-CD19 (anti CD19 CAR-T cells)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Single arm, open label, dose escalation: SHB-02-CD19 (anti CD19 CAR-T) | Experimental | anti CD19 CAR-T cells Receives: Drug: SHB-02-CD19 (anti CD19 CAR-T cells) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: From first dose to end 3 months post treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2026
- Study startJun 2026 (estimated)
- Primary completionJun 2029 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B Cell MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, open label, non-randomized trial
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Elad Jacoby, MD, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07503353
- Sponsor's protocol ID
- SHB-02-CD19
- Other IDs
- 2757-25-SMC
- Status last verified
- Mar 2026
- First submitted
- 25 Mar 2026
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Only IPD used in the results publication
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07503353
- Acronym / sponsor ID
- SHB-02-CD19
- Conditions
- B Cell Malignancies, Acute Lymphobkastic Leukemia, Non-Hodgekin Lymphoma (NHL-both Follicular & Diffuse Large Cell)
- Keywords
- ALL, DLBCL, NHL, CAR-T, CD-19
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- Jun 2026 (estimated)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 31 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, open label, non-randomized trial
| Arm | Type | Receives |
|---|---|---|
| Single arm, open label, dose escalation: SHB-02-CD19 (anti CD19 CAR-T) | Experimental | Drug: SHB-02-CD19 (anti CD19 CAR-T cells)anti CD19 CAR-T cells |
Who may qualify
- Ages
- 1 year to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- 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:
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Single arm, open label, dose escalation: SHB-02-CD19 (anti CD19 CAR-T) |
Primary outcome
Safety Evaluation: Treatment Related Toxicities
Time frame: From enrollment to 3 months post treatment.
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.
Efficacy Evaluation
Time frame: 1 month to 1 year post treatment.
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.
Minimal toxic dose evaluation
Time frame: From first dose to end 3 months post treatment.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Individual participant dataSharing planned: Yes. Only IPD used in the results publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SHB-02-CD19 (anti CD19 CAR-T cells) in people with B Cell Malignancies and Acute Lymphobkastic Leukemia, run by Sheba Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sivan Yakobi (972-03-5309046, sivan.yakobi@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Evaluation: Treatment Related Toxicities (time frame: From enrollment to 3 months post treatment.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.