CARPALL: Immunotherapy With CD19+CD22 CAR T-cells for CD19+ and CD22+ Acute Lymphoblastic Leukaemia

Inclusion Criteria: 1. Children and young adults (age 24 years or younger) with high risk/relapsed CD19+ and CD22+ acute lymphoblastic leukaemia with: 1. Resistant disease (\>5% blasts) at end of ALLTogether-1 protocol or equivalent induction 2. ALL with persisting high level MRD at 2nd time point of frontline national protocol (currently MRD \>10-4 at week 9 ALLTogether-1 Protocol or equivalent). 3. High risk infant ALL (age \< 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count \> 300 x 10\^9/L or poor steroid early response (i.e. circulating blast count \>1x10\^9/L following 7 day steroid pre-phase of induction as per national guidelines or equivalent) 4. Any patient with t(17,19) TCF3-HLF rearrangement 5. High risk 1st relapse (defined as very early (relapse within 18 months of diagnosis) and early relapses (any patient relapsing on therapy or within 6 months of completing treatment) and any relapse with high risk genetics, namely (KMT2A (MLL) rearrangements, low hypodiploidy/near haploidy, t(17;19)(q22;p13)/TCF3-HLF, iAMP21 and t(1;19)(q21;p13)/TCF3- PBX1, t(9;22)(34.1 q11.2)/BCR-ABL1 6. Any on therapy relapse in patients age 16-24 7. Any relapse of infant ALL 8. ALL post ≥ 2nd relapse 9. Any refractory relapse of ALL (defined as \> 1% blasts by flow cytometry after a at least 1 cycle of standard chemotherapy) 10. ALL with MRD \>10-4 prior to planned stem cell transplant 11. Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant 12. Any relapse of ALL after stem cell transplant as long as planned time of CD19+CD22CAR T cell infusion is \> 4 months post-transplant 13. Early (defined as \< 6 months post-infusion) loss of B cell aplasia or any CD19+CD22+ relapse following CD19CAR T cell therapy with Tisagenlecleucel Note patients with isolated CNS relapse meeting one or more of the criteria above are eligible for the study 2. Agreement to have a pregnancy test, use adequate contraception (if applicable) 3. Written informed consent Exclusion Criteria: Exclusion Criteria for registration: 1. Active Hepatitis B, C or HIV infection 2. Oxygen saturation ≤ 90% on air 3. Bilirubin \> 3 x upper limit of normal 4. Creatinine \> 3 x upper limit of normal 5. Women who are pregnant or breastfeeding 6. Stem Cell Transplant patients only: active significant (overall Grade ≥ II, Seattle criteria) acute GVHD or moderate/ severe chronic GVHD (NIH consensus criteria) requiring systemic steroids. 7. Inability to tolerate leucapheresis 8. Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≤ 50% 9. Pre-existing significant neurological disorder (other than CNS involvement of underlying haematological malignancy) 10. CD19 negative or CD22 negative disease Exclusion criteria for CD19+CD22CAR T-cell infusion: 1. Severe intercurrent infection at the time of scheduled CD19+CD22 CAR T-cell infusion 2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19+CD22 CAR T-cell infusion 3. Allogeneic transplant recipients with active significant acute GVHD overall grade ≥II or moderate/severe chronic GVHD requiring systemic steroids at the time of scheduled CD19+CD22 CAR T-cell infusion. Note: Such patients will be excluded until the patient is GVHD free and off steroids