Inclusion Criteria: 

• Documentation of relapsed or refractory CLL and SLL.
• 1. Cohort 1 and 2: Subjects with r/r CLL who have received at least 2 prior lines of treatment, one of which must include a BTK inhibitor
  2. Cohort 3: Subjects with r/r CLL and SLL must present with ≤ 1% circulating tumor cells in peripheral blood or ALC < 5000 cells/μL Subjects must have received at least 2 prior lines of treatment, one of which must include a BTK inhibitor.
  3. Cohort 4: Subjects with r/r CLL who have received at least 2 prior lines of treatment and must have received ibritunib as a single agent or in combination with anti-CD20 antibodies, BCL-2 inhibitors, and PI3k inhibitors. Subjects must have received ibrutinib  for at least 6 months as the last line of therapy prior to screening. Ibrutinib administration will continue up to 30 hours prior to leukapheresis. In case of treatment interruption with ibrutinib, the principal investigator should reach out to the medical monitor to discuss.
• An indication for treatment per IWCLL 2018 criteria (Appendix 2) and radiographically measurable disease (at least 1 lesion > 1.5cm in diameter).
• Adequate hematologic function as indicated by:
  • Platelet count ≥ 50 × 109/L;
  • Neutrophil count ≥ 0.5 × 109/L;
  • Hemoglobin ≥ 8 g/dL unless lower values are attributable to CLL.
• Adequate renal, hepatic, cardiac and pulmonary function defined as:
  • Creatinine clearance (as estimated by Cockroft-Gault) ≥ 60 mL/min;
  • Serum ALT/AST ≤ 2.5 x upper limit of normal (ULN);
  • Total bilirubin ≤ 1.5 mg/dL unless subject has Gilbert’s syndrome;
  • Left ventricular ejection fraction (LVEF) ≥50%, no evidence of pericardial effusion, no NYHA class III or IV functional classification, no clinically significant arrhythmias;
  • No clinically significant pleural effusion;
  • Baseline oxygen saturation > 92% on room air.
•  Age 18 or older.
• ECOG performance status of 0 or 1.
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy or BTKi (ibrutinib or acalabrutinib) at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists).

Exclusion Criteria: 

• A history of treatment including any of the following:
  • Prior CD19 directed therapy;
  • Treatment with alemtuzumab within 6 months before enrollment;
  • Allogeneic hematopoietic stem cell transplant (SCT) or donor lymphocyte infusion (DLI) within 6 months prior to enrollment;
  • Live vaccine administration within 4 weeks before enrollment;
  • Systemic immunosuppression or systemic treatment for any autoimmune disease not related to CLL in the 2 years before enrollment.
• Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index.
• History of autoimmune disease resulting in end-organ injury unless attributable to CLL (e.g., ITP, AIHA).
• Diagnosis of Richter’s transformation or a history of malignancy. Exceptions include:
  • Non-melanoma skin cancer or carcinoma in situ (eg, skin, cervix, bladder, breast);
  • Superficial bladder cancer;
  • Asymptomatic localized low grade prostate cancer for which watch-and-wait approach is standard of care;
  • Any other cancer that has been in remission for > 3 years prior to enrollment.
• History of severe hypersensitivity reaction attributed to aminoglycosides or any of the agents required for treatment in this study.
• CNS disease including:
  • Known presence of involvement by CLL/SLL;
  • History of any CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral edema with confirmed structural defects (eg, by whole-neuroaxis magnetic resonance imaging [MRI])
  • Note: Subjects with a history of seizures requiring antiseizure therapy are excluded.
• History of concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months before enrollment.
• History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment. Subjects taking prophylactic anticoagulants are eligible.
• Primary immunodeficiency.
• History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by  standard serological and genetic testing per current Infectious Disease Society of America (IDSA) guidelines or applicable country guidelines.
• Presence of active fungal, bacterial, viral infection or any infection requiring antimicrobial treatment for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with  the Kite medical monitor.
• Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are permitted.
• Women of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
• Subjects of child-bearing potential who are not willing to practice birth control from the time of consent through 6 months after the administration of conditioning chemotherapy or KTE-X19, whichever is longer.
• In the investigator’s judgment, subject is unlikely to complete all protocol-required study visits or procedures including follow-up visits or comply with requirements for participation.
• Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.