Phase Ia Study of a LentiGen® CD19 Chimeric Antigen Receptor (CAR) T Cells in Adult Patients With Relapsed/Refractory CD19 Positive Acute Lymphoblastic Leukemia (ALL) Using a Closed Transduction System
This is a Phase Ia, open label, dose finding single center trial designed to evaluate the maximum tolerated dose, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of CD19 CAR T cells targeting the B cell surface antigen CD19 following administration of chemotherapy lymphodepletion regimen in adults (age 18 - 75) with relapsed/refractory acute lymphoblastic leukemia (ALL).
• Patients aged between 18 to 75 years old (patients is older than 18.0 and less than 75.0 years old) 2. Signed informed consent form 3. Ability to comply with the study protocol 4. Relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL):
‣ Second or greater bone marrow (BM) relapse; or
⁃ Primary refractory, defined as not achieving complete remission (CR) after 2 cycles of a standard chemotherapy regimen, or Chemo-refractory, defined as not achieving CR after 1 cycle of standard chemotherapy for relapsed leukemia; or
⁃ Philadelphia chromosome-positive ALL intolerant of or with 2 failed lines of tyrosine kinase inhibitor (TKI) therapy; or
⁃ Relapsed patients ineligible for Allogeneic Stem Cell Transplant (AlloSCT) due to lack of a suitable donor.
⁃ Relapsed after AlloSCT. at least 12 weeks after alloSCT or relapse happened after withdrawing the post-transplant immunosuppression
⁃ Relapsed after prior CAR T cell and still CD19 positive. . (Patients with a history of ≥grade CRS, ≥ grade 3 ICANS, or severe hypersensitivity reactions following prior CAR T-cell therapy should be excluded.) 5. BM with ≥5% lymphoblasts by morphologic assessment at screening 6. For relapsed patients, documentation of CD19 tumor expression in BM or peripheral blood by flow cytometry or immunohistochemistry within 1 month of study entry 7. Patients with a history of CNS or meningeal involvement must be in a documented clinical remission prior to registration.
‣ 8\. Alanine aminotransferase (ALT) ≤5 times the upper limit of normal for age 9. Bilirubin ≤2 x ULN 10. Patients with good renal function defined as Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min.
‣ 11\. Absolute Neutrophil Count (ANC): Patients must have an ANC ≥ 1.0 x 109
‣ /L without the use of growth factors 12. Platelet Count: Patients must have a platelet count ≥ 50 x 109/L without transfusion support within 7 days of screening.
‣ 13\. Absolute Lymphocyte Count: Patients must have an absolute lymphocyte count ≥ 0.5 x 109/L.
‣ 14\. Definition of Adequate Organ Function:
∙ Renal Function: Glomerular Filtration Rate (GFR) \> 60mL/min.
∙ Hepatic Function: AST/ALT ≤ 5 x ULN and bilirubin ≤ 2 x ULN. Total bilirubin 1.5 ULN (except Gilbert's syndrome).
∙ Pulmonary Function: Adequate respiratory function defined as oxygen saturation ≥ 93% on room air.
∙ Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 45% by echocardiogram or MUGA scan and QTcF ≤ 480 ms. 15. Minimum level of pulmonary reserve defined as grade ≤1 dyspnea and pulse oxygenation \>93% on room air 16. Left ventricular ejection fraction ≥45% confirmed by echocardiogram within 30 days of screening 17. Karnofsky ≥ 70% and /or ECOG 0-2 at the time of screening 18. Women of child bearing age should have negative serum pregnancy test within 7 days prior to enrollment 19. If sexually active:
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‣ Females should use effective birth control 1 month prior to screening until 12 months after CAR T cell infusion
⁃ Males to use condom for six months after infusion 20. Meet institutional criteria to undergo leukapheresis or have an acceptable, stored leukapheresis product