Immunotherapy with CD19/22 CAR redirected T-cells for high risk/relapsed paediatric CD19+ and / or CD22+ acute lymphoblastic leukaemia and other haematological malignancies
Description
Design:
A multi-centre, non-randomised, open label phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children and young adults with high risk, relapsed CD19+ and/or CD22+ haematological malignancies (chiefly ALL and Burkitt’s lymphoma). 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) These are Chimeric Antigen Receptor (CAR) T-cells genetically modified to recognise the CD19 protein present on the malignant cells and attack them.
A total of 33 patients will be treated at 3 participating sites.
Treatment:
Patients will undergo an unstimulated leucapheresis which will be sent to GCT-GOSH for manufacture of CD19/22CAR T-cells. ATIMP manufacture takes about 15 days. During this period, patients may receive “holding” chemotherapy to maintain disease control.
Prior to CD19/22CAR T-cell infusion patients will receive lymphodepleting chemotherapy: fludarabine 30 mg/m2 iv day -7 to -3 and cyclophosphamide 0.5 g/m2 iv day -4 to -2 . A single dose of 106/kg cryopreserved CD19/22CAR+ T-cells will be administered intravenously. Patients will be followed up regularly (with daily, weekly and monthly visits) until 2 years post-CD19/22CAR T-cell infusion. After 2 years patients will continue to be followed up annually until 10 years post ATIMP infusion.
Key inclusion/exclusion criteria:
age 24 years or younger; diagnosis of high risk/relapsed CD19+ and/or CD22+ haematological malignancy. 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 the feasibility will be over 5.5 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/or CD22+ malignancies.