Anti-CD19 U-CAR-T Cell Therapy for B Cell Hematologic Malignancies

Study Overview
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Brief Summary
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The stunning response rate of anti-CD19(cluster of differentiation antigen 19) auto-CAR(chimeric antigen receptor)-T cell therapy brings hope to patients with relapsed or refractory B-cell hematologic malignancies. However, based on open clinical trials, using patients' T cells might encounter the failure of apheresis available T cells, even if successful, the time needed for the manufacture could also cause the irreversible disease progress. Furthermore, the cost of auto-CAR-T cells is not affordable for most patients. So to provide an accessible and affordable anti-CD19 CAR-T cell therapy for patients with B-cell hematologic malignancies, we launch such a trial that using the edited T cells from healthy donors to manufacture universal CAR-T cells and adapt it in patients with CD19+ B-cell leukemia or lymphoma.

Official Title
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Anti-CD19 Universal CAR-T Cells for CD19+ B Cell Hematologic Malignancies: a Multi-center, Uncontrolled Trial

Conditions
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B-cell Acute Lymphoblastic Leukemia, B-cell Lymphoma

Intervention / Treatment
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* Biological: anti-CD19 UCAR-T cells
* Drug: Fludarabine
* Drug: Cytoxan
* Drug: Melphalan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Diagnosis of recurrent B-cell acute lymphoblastic leukemia (B-ALL), B-cell acute lymphoblastic lymphoma (B-LLy), or B-non-Hodgkin lymphoma (B-NHL) 2. CD19-positive tumor (≥20% CD19 positive blasts by flow cytometry or immunohistochemistry (tissue)） 3. Hgb ≥ 7.0 (can be transfused) 4. Life expectancy greater than 12 weeks 5. Informed consent explained to, understood by and signed by the patient/guardian. The patient/guardian is given a copy of informed consent. Exclusion Criteria: Pregnant or lactating. Tumor in a location where enlargement could cause airway obstruction (per investigator discretion). Active infection with HIV or HTLV. Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment). CNS abnormalities: Presence of CNS(central nervous system)-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF(cerebrospinal fluid) with ≥ 5 WBC( white blood cell)s per mm3 (unless negative by the Steinherz/Bleyer algorithm); Presence of any CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 70 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: anti-CD19 UCAR-T cells<br>After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD19 UCAR-T cells between 1 and 5 ×10^7 cells/Kg will be evaluated | Biological: anti-CD19 UCAR-T cells<br>* Dose range:1 to 5 ×10^7 cells/Kg, Dose level one: 1×10^7 cells/Kg, Dose level two: 3×10^7 cells/Kg, Dose level three:5 ×10^7 cells/Kg<br>Drug: Fludarabine<br>* 30mg/m^2 per day for 6 days<br>Drug: Cytoxan<br>* 300mg/m^2 per day for 2 to 6 days determined by tumor burden at baseline<br>Drug: Melphalan<br>* 50 to 70 mg/m^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the anti-tumor efficiency of anti-CD19 UCAR-T cells | ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value | 4 weeks after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the long-term efficiency of anti-CD19 UCAR-T cells | ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value | 3 and 6 months after infusion |