TT52CAR19 Therapy for B-cell Acute Lymphoblastic Leukaemia (B-ALL)

Inclusion criteria

• Patients with relapsed (second or subsequent bone marrow relapse or bone marrow relapse after allo-SCT) or refractory (not achieving an initial complete response (CR) after 2 cycles of standard chemotherapy) CD19-positive B-acute lymphoblastic leukaemia
• Morphologically confirmed with leukemic blasts in the bone marrow or a quantifiable MRD load of 1x10-4 (by multiparameter flow cytometry and/or quantitative polymerase chain reaction)
• 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 Karnofsky (age ≥ 16 years at the time of assent/consent) performance status ≥ 50 Eastern Cooperative Oncology Group ECOG performance status < 2

Exclusion criteria

• Patients/parents unwilling to undergo a follow-up for 15 years
• Foreseeable poor compliance to the study procedures
• CD19-negative B-cell leukaemia
• Evidence of disease progression after cytoreduction
• Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer National guidelines). Patients developing grade 3 CNS disease at any time after enrolment will be excluded.
• Absence of suitable HLA matched or mismatched donor
• Weight < 6 kgs
• Presence of donor-specific anti-HLA antibodies directed against PBLTT52CAR19
• GvHD requiring systemic therapy
• Systemic steroid therapy prednisolone >0.5mg/kg/day
• Known hypersensitivity to any of the test materials or related compounds
• Active bacterial, fungal, or viral infection not controlled by a 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.
• 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.
• Lactating female participants unwilling to stop breastfeeding
• Intrathecal methotrexate within 4 weeks or intrathecal chemotherapy (e.g Ara-C) within 2 weeks of lymphodepletion
• Less than 2 half-lives from prior therapy with immune checkpoint pathway modifiers to lymphodepletion
• Prior CAR19 therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity