This study aims to evaluate the safety, efficacy and duration of response of CD19+CD22 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in children with high risk, relapsed CD19+ and CD22+ acute lymphoblastic leukaemia
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
Active Hepatitis B, C or HIV infection
Oxygen saturation ≤ 90% on air
Bilirubin > 3 x upper limit of normal
Creatinine > 3 x upper limit of normal
Single group
Leukapheresis
Procedure/SurgeryPatients will undergo an unstimulated leukapheresis to isolate the required immune cells to produce the CD19+CD22 CAR T-cells
Total Body Irradiation (TBI)
RadiationParticipants will receive low-dose total body irradiation delivered as a single fraction on day -7 prior to CD19+CD22CAR T-cell infusion.
Lymphodepletion with Fludarabine
DrugPatients will receive lymphodepleting chemotherapy with iv fludarabine on days -6 to -3 prior to CD19+CD22CAR T-cell infusion.
Lymphodepletion with Cyclophosphamide
DrugPatients will receive lymphodepleting chemotherapy with iv cyclophosphamide on days -6 to -5 prior to CD19+CD22CAR T-cell infusion.
CD19+CD22 CAR T-cells
Biological/Vaccine1 dose of CD19+CD22 CAR T-cells given as an intravenous injection through a Hickman line or PICC line (peripherally inserted central catheter) on day 0.
Incidence of unacceptable toxicity following CD19+CD22 CAR T-cell infusion
The incidence of unacceptable toxicity occurring within 28 days of CD19+CD22CAR T-cell infusion.
Molecular remission
Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 28 days post CD19+CD22CAR T-cell infusion will be determined.
Feasibility of Generation of CD19+CD22 CAR T-cells
Evaluated by the number of therapeutic products generated.
Molecular Remission
Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 3 months post CD19+CD22CAR T-cell infusion will be determined.
Long-Term Molecular Remission
Number of patients in molecular remission without further therapy at 1 and 2 years
Duration of Response
Duration of response is measured from the time of achieving molecular remission or flow MRD negativity until the disease relapse or death, whichever occurs first.
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