Phase I study of base-edited CAR T cells against acute myeloid leukaemia (AML): deep conditioning ahead of allogeneic stem cell transplantation
Paediatric relapsed CAR33+ acute myeloid leukaemia
In this study, all patients will receive a single dose of a CAR33+ T cell treatment (BE CAR-33) given through an intravenous infusion. The amount of BE CAR-33 T cells given will be based on the patient's weight, and the treatment will last for 28 days. There will be no randomization of patients, and patients will be followed up for 12 months after the treatment.
Demographic characteristics: 1. Male or female patients 2. Age ranging between 6 months and <16 years old Medical and therapeutic criteria: 1. Relapsed AML ahead of planned allogeneic haematopoietic stem cell transplantation (allo-SCT). Morphologically confirmed with leukemic blasts in the bone marrow (>5%) or a quantifiable minimal residual disease (MRD) load (by multiparameter flow cytometry and/or quantitative polymerase chain reaction) 2. CD33+ (>95%) blast leukaemia associated immunophenotype (LAIP) 3. Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available 4. Estimated life expectancy ≥ 12 weeks 5. Lansky (age < 16 years at the time of assent/consent) and Eastern Cooperative Oncology Group ECOG performance status < 2
1. Patients/parents unwilling to undergo a follow-up for 15 years 2. Foreseeable poor compliance to the study procedures 3. Evidence of disease progression after cytoreduction 4. Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer Network guidelines 5. Absence of suitable HLA matched or mismatched donor 6. Weight <6 kgs 7. Presence of donor-specific anti-HLA antibodies directed against BE-CAR33 8. GvHD requiring systemic therapy 9. Systemic steroid therapy prednisolone >0.5mg/kg/day 10. Known hypersensitivity to any of the test materials or related compounds 11. Active bacterial, fungal or viral infection not controlled by standard of care anti-microbial or anti-viral treatment. Uncontrolled bacteraemia/ fungaemia is defined as the ongoing detection of bacteria/fungus on blood cultures despite antibiotic or anti-fungal therapy. Uncontrolled viraemia is defined as rising viral loads on two consecutive occasions despite antiviral therapy. 12. Risk of pregnancy or non-compliance with contraception (if applicable). Girls of childbearing potential must have been tested negative in a pregnancy test within 14 days prior to inclusion. 13. Lactating female participants unwilling to stop breastfeeding 14. Prior CAR T cell therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity