Intravenous Autologous CD19 CAR-T Cells for R/R B-ALL

Recruitment & Eligibility

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.

Study & Design

Arm && Interventions

Group	Intervention	Description
CD19 CAR-T CELLS	CD19 CAR-T CELLS	A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
CD19 CAR-T CELLS	Fludarabine	A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
CD19 CAR-T CELLS	Cyclophosphamide	A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	Participants will be followed for the duration of the treatment, with an expected average of 3 months.	Overall Response Rate (ORR) defined as Complete Response (CR) and CR with incomplete blood recovery (CRi) according to WHO criteria.
CR with incomplete blood recovery (CRi).	12 Months	Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.
Complete response (CR)	12 Months	Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	12 Months, 24 Months	Overall Survival (OS) defined as the time from treatment to the date of death due to any cause.
Progression free survival (PFS)	12 Months, 24 Months	Progression Free Survival (PFS) defined as the time from treatment to first documentation of objective leukemic progression (date of leukaemia assessment documenting progressive disease) or to death due to any cause. Progression is assessed by BM biopsy or CSF analysis according to NCCN criteria. It is assessed at Day 30 and monthly thereafter, or earlier if clinically indicated.
Time to next treatment (TTNT)	12 Months, 24 Months	Time To Next Treatment (TTNT) defined as the end of study treatment until the institution of the next therapy.
Percentage of adverse events	30 days	Percentage of participants with adverse events

Recruitment & Eligibility