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.
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.
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.
Single group
SHB-02-CD19 (anti CD19 CAR-T cells)
DrugPhase 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.
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.
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.
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.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
