Chimeric Antigen Receptor T Cells (CART) Therapy in Refractory/Relapsed B Cell Hematologic Malignancies

Study Overview
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Brief Summary
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This single arm, open-label, multi-center clinical trial is studying CD19 targeted chimeric antigen receptor T cells therapy in treating patients with CD19 positive malignant B-cell derived leukemia and lymphoma that is relapsed (after stem cell transplantation or chemotherapy) or refractory to chemotherapy.

Detailed Description
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This single arm, open-label, multi-center clinical trial is studying CD19 targeted chimeric antigen receptor T cells therapy in treating patients with CD19 positive malignant B-cell derived leukemia and lymphoma that is relapsed (after stem cell transplantation or chemotherapy) or refractory to chemotherapy. When patients enroll in this trial, autologous CD19CART cells were generated from the mononuclear cells of the patient's peripheral blood (PB). During the term of cell preparation of CD19CART cells, patients will receive a conditioning regimen. One day after completing conditioning regimen, the patient will be given infusions of CD19CART cells into the vein over a period of 1 to 3 days. Patients will be monitored for a response, toxic effects, and the expansion and persistence of circulating CD19CART cells.

Official Title
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A Multicenter Efficacy and Safety Study of Cluster of Differentiation 19 (CD19)-Targeted CART (CD19CART) Therapy for CD19 Positive Relapsed or Refractory B-cell Hematologic Malignancies (SCT019-01）

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

Intervention / Treatment
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* Biological: CD19CART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed as CD19 positive refractory and relapsed B cell hematologic malignancies included acute lymphoblastic leukemia (ALL),chronic lymphocytic leukemia(CLL),non-Hodgkin's lymphoma(NHL) not eligible or appropriate for auto-HSCT or allo-HSCT or relapsed after hematopoietic stem cell transplant(HSCT) At least one measurable lesion defined as one lesion larger than 1.5cm or two lesion more than 1.0cm(for patients with NHL ) Age ≤60 years Eastern Cooperative Oncology Group(ECOG) Performance status 0 to 2, Expected survival > 6 months Left Ventricular Ejection Fraction (LVEF) > 50% no history of other malignancies; no other serious diseases which conflict with the treatment in the present trial All patients should consent to adopt efficient contraception methods during the treatment and after the treatment. The pregnant tests of women who are in child bearing period should be negative before the treatment. patients should understand and are willing to participate in the trial. Inform consent form is supposed to obtained before treatment Exclusion Criteria: Diagnosis or classification undefined Those with primary central nervous system lymphoma or testicular leukaemia or lymphoma Patients with a known history or prior diagnosis of epilepsia or other disease affecting the central nervous system, or serious mental diseases; Patients who have secondary leukaemia or lymphoma after chemotherapy or radiotherapy for other malignancies Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy, concurrent use of immunosuppressant medications Class III/IV cardiovascular disability according to the New York Heart Association Classification Pregnant or lactating women(the safety of this therapy on unborn children is not known) With active infection Active hepatitis B, hepatitis C or syphilis infection Patients use of systemic steroids within 2 weeks. Recent or current use of inhaled steroids is not exclusionary Prior treatment with gene therapy product Cluster of differentiation 3(CD3) positive cells<0.9x10^4/ml in peripheral blood (PB) Organ function meeting following criteria: liver and renal function: alanine aminotransferase(ALT)/aspartate aminotransferase(AST) > 3 times the upper limit of normal, or bilirubin>2.0 mg/dl（34.2umol/L）, or creatinine >2.5mg/dl（221.0umol/L） ; hematopoietic function:Neutrophil count<1.0x10^9/L，hemoglobin<80g/L，platelet <50x10^9/L(for patients with NHL ) Any uncontrolled active medical disorder that would preclude participation as outlined HIV infection The researchers considered unsuitable to participate in this clinical study. Patients with poor compliance

Ages Eligible for Study
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Maximum Age: 60 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: single arm<br>Experimental: CD19 CART cell.The target dose range administered in this study is 1x10e5-1x10e7 CART-19 cells/kg. | Biological: CD19CART<br>* Patients will be given infusions of CD19CART cells into the vein over a period of 1 to 3 days. The target dose range administered in this study is 1x10e5-1x10e7 CD19CART cells/kg. Patients will be monitored for a response, toxic effects, and the expansion and persistence of circulating CD19CART cells.<br>* Other names: CD19-directed chimeric antigen receptor modified T cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of study related adverse events |  | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-leukemia or lymphoma responses to CD19CART cell infusions |  | up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed, refractory, CD19+, leukemia, lymphoma