Title
Intravenous Autologous CD19 CAR-T Cells for R/R B-ALL
A Phase II/III Prospective, Open Label Study to Evaluate Safety and Efficacy of Intravenous Autologous CD19 CAR-T Cells for Relapsed/ Refractory B-Acute Lymphoblastic Leukaemia
Phase
Phase 2/Phase 3Lead Sponsor
National University of MalaysiaStudy Type
InterventionalStatus
RecruitingIndication/Condition
Refractory B Acute Lymphoblastic Leukaemia Relapsed B Acute Lymphoblastic LeukaemiaIntervention/Treatment
CD19 CAR-T CELLS Cyclophosphamide FludarabineStudy Participants
10This is Phase II / III, Prospective, single arm, Open Label Study to Evaluate Safety and Efficacy of Intravenous Autologous CD19 CAR-T Cells for Relapsed / Refractory B-Acute Lymphoblastic Leukaemia
CD19 CAR-T cells will be administered after completion of the chemotherapy.
Patients will receive lymphodepleting chemotherapies consisting Cyclophosphamide 250mg/m2/day IV(Day -5, Day -4, Day -3 ).
Patients will receive lymphodepleting chemotherapies consisting of Fludarabine 25mg/m2/day IV (Day -5, Day -4, Day -3 ).
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
Inclusion Criteria: Patients with relapsed/refractory B-ALL in accordance with World Health Organization (WHO) classification by virtue of BM morphology, flow cytometry, cytogenetics and molecular genetics Age between ≥13 to ≤ 65 years No detectable leukaemia in the CSF (CNS-1) CNS leukaemia without clinically evident neurological symptoms (CNS-2; with <5 WBC per μL and cytology positive for blasts) Adequate organ function as defined by a creatinine clearance > 50 ml/min, serum total bilirubin < 5 times the normal value, left ventricular ejection fraction > 40% ECOG performance status ≤ 2 Life expectancy > 3 months Post allogeneic HSCT must be ≥ Day +100 with no evidence of active GVHD and not receiving immunosuppression Female patients of child bearing age must have negative pregnancy test and is on highly effective contraception methods Male patients must use highly effective contraception methods Exclusion Criteria: Patients with CNS-3 leukaemia. Active cancer (other than B-ALL). Evidence of severe lung, heart (NYHA class III/IV, arrhythmia, AV block, uncontrolled hypertension), liver, or renal failure or severe neurologic disorder. Presence of active autoimmune disease or atopic allergy. HIV serology positivity. Active Hepatitis B or C infection as evidenced by quantitative viral PCR assay. Uncontrolled sepsis Pregnant / nursing female. Ongoing prednisolone > 1mg/kg daily or equivalent. Chemotherapy immunotherapy in the recent 4 weeks such as allogeneic cellular therapy weeks, anti-GVHD therapy.
