Immunotherapy with CD19+CD22 CAR redirected T-cells for high risk/relapsed paediatric CD19+ and CD22+ acute lymphoblastic leukaemia
Description
Design:
A multi-centre, non-randomised, open label phase I clinicaltrial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children and young adults with high risk, relapsed CD19+ and CD22+ acute lymphoblastic leukaemia.
- The ATIMP tested in cohort 1 and 2 of this study is CD19CAT-41BBζ CAR T-cells (referred to as CD19CAR T-cells).
- The ATIMP tested in cohort 3 of this study is CD19CAT-CD22 9A8-41BBZ CAR T-cells (referred to as CD19/22CAR T-cells).
- The ATIMP tested in cohort 4 of this study is CD19CAT-41BBZ + CD22 9A8-41BBZ CAR T-cells (referred to as CD19+CD22CAR T-cells).
These are Chimeric Antigen Receptor (CAR) T-cells genetically modified to recognise the CD19 or CD22 proteins present on the malignant cells and attack them.
A total of 33 patients were treated across 3 participating sites in cohorts 1-3. A further 12 patients will be treated in cohort 4.
Treatment:
- Leucapheresis: Patients will undergo an unstimulated leucapheresis which will be sent to C+GTS-GOSH for manufacture of CD19+CD22CAR T-cells.
- Lymphodepletion: Prior to CD19+CD22CAR T-cell infusion patients will receive a single fraction of low dose total body irradiation on day -7 and lymphodepleting chemotherapy: fludarabine and cyclophosphamide.
- CD19+CD22CAR T-cell Infusion: The CD19+CD22CAR T-cells will be administered intravenously as a split dose on day 0 and 14. Two dose levels will be tested.
- Follow-Up: Patients will be followed up regularly (with daily, weekly and monthly visits) until 2 years post-CD19+CD22CAR T-cell infusion. After 2 years patients will continue to be followed up annually until 15 years post ATIMP infusion.
Key inclusion/exclusion criteria:
age 24 years or younger; diagnosis of high risk/relapsed CD19+ and CD22+ acute lymphoblastic leukaemia. Patients with active HepB, HepC or HIV infection; with acute or chronic GVHD requiring steroids are excluded from the study. Creatinine and bilirubin need to be no more than 3xULN.
Duration of recruitment:
Anticipated recruitment for cohort 4 is 1.5 years.
Aim
The aim of the study is to evaluate the safety, efficacy and duration of response of the CAR T-cells in children and young adults with high risk / relapsed CD19+ and CD22+ acute lymphoblastic leukaemia.