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

Más betegség

• 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.

Laborértékek

• 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
• Hepatic dysfunction, defined as bilirubin > x2 upper normal limit (except when explained by hemolysis or Gilbert) or SGOT > x2.5 upper normal limit.

Egyéb

• Pregnant or breast-feeding females

• 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
• 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.