Phase 1 Study of Base Edited CAR T Cells Against AML: Deep Conditioning Ahead of Allogeneic Stem Cell Transplantation
In this phase 1 clinical trial, the investigators are testing an experimental medicine in children aged 6 months up to 16 years with acute myeloid leukaemia (AML), which has come back (relapsed). The new product is made from white blood cells (T cells) collected from a healthy donor and changed so they can kill leukaemia cells. These 'ready-made' CAR T cells have been made using a new technique called Base Editing to modify their DNA code and have been given the code name 'BE CAR-33'. This technique allows them to work after chemotherapy and also disarms them to prevent effects against normal cells. The main purpose of this study is to assess the safety of the 'BE CAR-33' therapy and to see if ready-made CAR T cells can get rid of Acute Myeloid Leukaemia ahead of a planned bone marrow transplant that will hopefully prevent the leukaemia from returning.
• Male or female patients
• Age ranging between 6 months and \<16 years
⁃ Medical and therapeutic criteria
• Relapsed AML ahead of scheduled allogeneic haematopoietic stem cell transplantation (allo-SCT).
• Morphologically confirmed with leukemic blasts in the bone marrow (\>5%) or a quantifiable MRD by multiparameter flow cytometry and/or quantitative polymerase chain reaction (\>10-4)
• CD33+ leukaemia associated immunophenotype (LAIP) on \>95% of blasts
• Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available
• Estimated life expectancy ≥ 12 weeks
• Lansky (age \< 16 years at the time of assent/consent) or performance status ≥ 70;
• Eastern Cooperative Oncology Group ECOG performance status \< 2.