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

Study Overview
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Brief Summary
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This 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

Official Title
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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

Conditions
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Relapsed B Acute Lymphoblastic Leukaemia, Refractory B Acute Lymphoblastic Leukaemia

Intervention / Treatment
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* Biological: CD19 CAR-T CELLS
* Drug: Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD19 CAR-T CELLS<br>A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously. | Biological: CD19 CAR-T CELLS<br>* CD19 CAR-T cells will be administered after completion of the chemotherapy.<br>Drug: Cyclophosphamide<br>* Patients will receive lymphodepleting chemotherapies consisting Cyclophosphamide 250mg/m2/day IV(Day -5, Day -4, Day -3 ).<br>Drug: Fludarabine<br>* Patients will receive lymphodepleting chemotherapies consisting of Fludarabine 25mg/m2/day IV (Day -5, Day -4, Day -3 ).<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overall Survival (OS) defined as the time from treatment to the date of death due to any cause. | 12 Months, 24 Months | 
| Progression free survival (PFS) | 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. | 12 Months, 24 Months | 
| Time to next treatment (TTNT) | Time To Next Treatment (TTNT) defined as the end of study treatment until the institution of the next therapy. | 12 Months, 24 Months | 
| Percentage of adverse events | Percentage of participants with adverse events | 30 days |