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