XLCART001 Treatment in Relapsed/Refractory/High-risk B-cell Malignancy Subjects

Study Overview
=================
Brief Summary
-----------------
The trial is a single arm, single-center, non-randomized clinical trial which is designed to evaluate the efficacy and safety of XLCART001 in treatment of relapsed/refractory/high-risk B-cell malignancy subjects

Official Title
-----------------
A Single-center, Open Study Evaluating Efficacy and Safety of XLCART001（CD-19） Treatment in Relapsed/Refractory/High-risk B-cell Malignancy Subjects

Conditions
-----------------
Lymphoma, B-Cell, Leukemia, B-cell

Intervention / Treatment
-----------------
* Biological: chimeric antigen receptor T cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years, male and female, Confirmed as CD19-positive B cell lymphoma/leukemia by immunohistochemistry or flow cytometry No effective treatment Patients must have a measurable or evaluable disease at the time of enrollment. Adequate organ system function including: ALT/AST < 3 upper limit of normal; Total Bilirubin < 2.5 upper limit of normal Creatinine < 2 upper limit of normal Oxygen saturation ≥ 95% Left ventricular ejection fraction ≥ 40% Number of neutrophil ≥ 0.75×10^9/L, number of platelet ≥ 50×10^9/L At least 4 weeks from receiving previous treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments) No contraindications of peripheral blood apheresis Female subjects in childbearing age, their serum or urine pregnancy test must be negative. All patients must agree to take effective contraceptive measures during the trial measures ECOG score 0-2, expected survival ≥ 12 weeks Exclusion Criteria: Women who are pregnant or lactating. Patients have breeding intent in 12 months or cannot take effective contraceptive measures during the trial measures Uncontrollable active infection within four week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible. Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons Subjects with any autoimmune disease or any immune deficiency disease Have a history of allergy to antibodies or cellular products Participated in any other clinical trial within four weeks Used of systemic steroids within four weeks (using inhaled steroids or ≤ 20mg/d prednison are exceptions) Have mental diseases Have history of drug addiction The investigators believe that any increase in the risk of the subject or interference with the results of the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: chimeric antigen receptor T cells|Dose CAR+ cells/kg B-cell lymphoma 4×10^6 Acute lymphocytic leukemia 2×10^6 Chronic lymphocytic leukemia 10×10^6|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Overall response rate (ORR) = complete response (CR) rate + partial response (PR) rate, ORR will be assessed at weeks 12. | 12 weeks | 
| Overall Survival | from the time of enrollment to death from any cause or the date of the last follow-up visit | 6 months,1 year, 2 years | 
| Progression-free Survival | the time from enrollment to disease progression, death from any cause, or the date of the last follow-up visit | 12 weeks,6 months,1 year, 2 years | 
| Event-free Survival | the time from enrollment to any events, or the date of the last follow-up visit | 12 weeks,6 months,1 year, 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Non-haematological dose-limiting toxicities was any toxicity of grade 3 or higher occurring within 28 days of XLCART001 infusion judged possibly related to the treatment regimen.The following toxicities were not considered dose limiting toxicities: tumor lysis syndrome, abnormal electrolytes responding to supplementation, hypoalbuminemia, liver dysfunction resolving to ≤grade 2 within 14 days, transient (<72 hours) grade 4 hepatic enzyme abnormality, and grade 3 or 4 fever or neutropenic fever. | 28 days | 
| Number of CAR-T cells | The number of CAR-T cells detected by flow cytometry and copy number of CAR-T cells tested by polymerase chain reaction | Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28, 8 weeks, 12 weeks, 6 months, 1 years, 2 years | 
| Duration of CAR-T cells | The duration of CAR-T cells detected by flow cytometry and copy number of CAR-T cells tested by polymerase chain reaction | Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28, 8 weeks, 12 weeks, 6 months, 1 years, 2 years |