CD19 CAR and PD-1 Knockout Engineered T Cells for CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma

Inclusion Criteria:

* 1.Children and adults (age 70 years or younger) with high risk/relapsed CD19+ haematological malignancy:

  1. Resistant disease (\>25% blasts) at end of UKALL 2011 or equivalent induction
  2. ALL with persistent high level MRD at 2nd time point of frontline national protocol (currently \> 5 x 10-3 at week 14 UKALL2011 or equivalent)
  3. High risk infant ALL (age \< 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count \> 300 x 109/L or poor steroid early response (i.e circulating blast count \>1x109/L following 7 day steroid pre- phase of Interfant 06)
  4. Intermediate risk infant ALL with MRD \> 10-3 at end of Interfant06 induction
  5. Very early (\< 18 months from diagnosis) bone marrow or extramedullary relapse of acute lymphoblastic leukaemia (ALL)
  6. Early (within 6 months of finishing therapy) bone marrow, or combined extramedullary relapse of ALL with bone marrow minimal residual disease (MRD) \> 10-3 at end of re-induction
  7. Any on therapy relapse of ALL in patients age 16-70
  8. Any relapse of infant ALL
  9. ALL post ≥ 2nd relapse
  10. Any refractory relapse of ALL
  11. ALL with MRD \>10-4 prior to planned stem cell transplant
  12. Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant
  13. Any relapse of ALL after stem cell transplant
  14. Any relapse of Burkitt's or other CD19+ lymphoma
* 2.Agreement to have a pregnancy test, use adequate contraception (if applicable)
* 3.Written informed consent

Exclusion Criteria:

* Exclusion Criteria for registration:

  1. CD19 negative disease
  2. Active hepatitis B, C or HIV infection
  3. Oxygen saturation ≤ 90% on air
  4. Bilirubin \> 3 x upper limit of normal
  5. Creatinine \> 3 x upper limit of normal
  6. Women who are pregnant or lactating
  7. Stem Cell Transplant patients only: active acute graft-versus-host disease (GVHD) overall Grade ≥ II (Seattle criteria) or moderate/severe chronic GVHD (NIH consensus criteria) requiring systemic steroids
  8. Inability to tolerate leucapheresis
  9. Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≤ 50%
* Exclusion criteria for CD19CAR T-cell infusion:

  1. Severe intercurrent infection at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
  2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
  3. Allogeneic transplant recipients with active acute GVHD overall grade \>2 or moderate/severe chronic GVHD requiring systemic steroids at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion