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

Prior treatment

• 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.
• 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

Other illness

• Active Hepatitis B, C or HIV infection
• Pre-existing significant neurological disorder (other than CNS involvement of underlying haematological malignancy)
• CD19 negative or CD22 negative disease
• Severe intercurrent infection at the time of scheduled CD19+CD22 CAR T-cell infusion

Lab values

• Bilirubin \> 3 x upper limit of normal
• Creatinine \> 3 x upper limit of normal

Age

• Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≤ 50%

Other

• Oxygen saturation ≤ 90% on air
• Women who are pregnant or breastfeeding
• Inability to tolerate leucapheresis
• Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19+CD22 CAR T-cell infusion

• Children and young adults (age 24 years or younger) with high risk/relapsed CD19+ and CD22+ acute lymphoblastic leukaemia with:
  • Resistant disease (\>5% blasts) at end of ALLTogether-1 protocol or equivalent induction
  • 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).
  • 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)
  • Any patient with t(17,19) TCF3-HLF rearrangement
  • 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
  • Any on therapy relapse in patients age 16-24
  • Any relapse of infant ALL
  • ALL post ≥ 2nd relapse
  • Any refractory relapse of ALL (defined as \> 1% blasts by flow cytometry after a at least 1 cycle of standard chemotherapy)
  • ALL with MRD \>10-4 prior to planned stem cell transplant
  • Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant
  • Any relapse of ALL after stem cell transplant as long as planned time of CD19+CD22CAR T cell infusion is \> 4 months post-transplant
  • 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
• Agreement to have a pregnancy test, use adequate contraception (if applicable)
• Written informed consent