CD19 CAR T Cells in Children and Adults With Relapsed or Refractory CD19 Positive B Cell Malignancies

Inclusion Criteria

• •1. Subjects must have the ability to understand and the willingness to sign a written informed consent document
• •2. Stated willingness to comply with all study procedures and availability for the duration of the study
• •3. Male or female, between the age of 1 and 65 years
• •4. In good general health as evidenced by medical history and diagnosed relapsed or refractory CD19+ B cell malignancies including acute lymphocytic leukemia (ALL), non-Hodgkin's lymphoma containing Diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), or small lymphocytic lymphoma (SLL), B-cell prolymphocytic leukemia(BPLL), Lymphoplasmacytic Lymphoma, Marginal Zone Lymphoma (MZL).
• •5. Definition of relapse or refractory as below:
• •* Ineligible hematopoietic transplantation
• •* Relapse after transplantation
• •* Subject with ALL was evaluated by minimal residual disease \> 0.1% after treatment with at least two lines of therapy. Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) treated by at least two lines of therapy, including tyrosine kinase inhibitors (TKIs) are eligible.
• •* Subject with lymphoma treated regimens containing both anti-CD20 antibody and anthracycline-containing chemotherapy regiment. Subjects with transformed follicular lymphoma must have received prior chemotherapy for follicular lymphoma and subsequently have the chemo refractory disease after transformation to diffuse large B-cell lymphoma
• •6. The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available.
• •7. Performance status: Adult Subjects: ECOG ≤2; Subjects \> 10 years of age: Karnofsky≥ 50%; Subjects ≤ 10 years of age: Lansky scale ≥ 50% (See Appendix 1)
• •8. The following laboratory values :
• •* Total bilirubin ≤ 2x upper limit of normal
• •* AST (SGOT) ≤ 5x upper limit of normal
• •* ALT (SGPT) ≤ 5x upper limit of normal
• •* Serum Creatinine ≤ 2.0 mg/dl
• •* Subjects must have the following hematologic function parameters (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion):
• •i.Absolute lymphocyte count\>0.3× 109cells/L ii.Platelets\>50 × 109 cells/L
• •9. Prior therapy wash-out: At least 2 weeks or 5 half-lives, whichever is longer, must have elapsed since any prior systemic therapy including cytotoxic chemotherapy, immunomodulatory, immunosuppressive, antiproliferative drugs, antibody, immune checkpoint therapy, pegylatedasparaginase, pegfilgrastimat the time the subject is planned for leukapheresis. Filgrastim, intrathecal methotrexate, systemic steroid, and donor lymphocyte infusion must be stopped 5 days, 7 days, 72 hours, and 4 weeks before leukapheresis, respectively.
• •10. Ability to take oral medication and be willing to adhere to the intervention protocols and medication regimens
• •11. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during the follow-up period of the protocol
• •12. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner