Safety and Efficacy Evaluation of CD19-UCART

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ascending doses of CD19-UCART in patients with relapsed or refractory B-cell hematological malignancies.

Detailed Description
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CD19-UCART is a kind of off-the-shelf product originated from health donor's PBMC.This is a open-label, dose estilation study to evaluate the safety and anti-tumor efficacy of CD19-UCART in the treatment of relapsed or refractory B-cell hematological malignancies.

Official Title
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A Safety and Efficacy Study of CD19-UCART (Allogeneic Engineered T-cells Expressing Anti-CD19 Chimeric Antigen Receptor) in Patients With Relapsed or Refractory B-cell Hematologic Malignancies

Conditions
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Acute Lymphoblastic Leukemia (ALL), Non Hodgkin Lymphoma (NHL)

Intervention / Treatment
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* Biological: CD19-UCART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily participating in this clinical study and signing the informed consent form; The estimated survival period is at least one month; No other serious cardiopulmonary diseases, and normal liver and kidney functions (except for subjects with tumor lesions in their liver and kidneys); Failure of T cell isolation during autologous CART preparation or failure of CART amplification or failure to complete apheresis or disease progression resulting in patients not benefiting from autologous CAR-T cell therapy; Or: T cell percentage in PBMC of peripheral blood ≤ 10%; Or the disease is not effectively controlled within one month after autologous CAR-T transfusion, and the patient cannot receive CAR-T transfusion again; Flow cytometry within two months demonstrated positive expression of CD19 in the tumor (positive rate 50%-90%; Or biopsy ≥ 50% within 6 months; Or obtaining a biopsy again); Hematological indicators: 1) WBC count ≥ 1.5× 10^9/L; Absolute value of neutrophils ≥ 0.8× 10^9/L; Lymphocyte count ≥0.1×10^9/L;2) Hemoglobin ≥ 60g/L;3) Platelet count ≥20×10^9/L; Biochemical indicators (except for subjects with tumor foci in liver and kidney): Total bilirubin (TBIL)≤1.5 times the Upper Limits of Normal (ULN); AST and ALT≤1.5 *ULN; Scr and BUN)≤1.5*ULN; Biochemical indicators in subjects with liver and kidney invasion should meet: Total bilirubin (TBIL)≤5 *ULN;AST and ALT≤5*ULN; Scr and BUN ≤ 5*ULN; Cardiac function: Good hemodynamic stability, and the left ventricular ejection fraction (LVEF) ≥ 55%; Serum viral EBV-DNA, CMV-DNA, HIV antibody and syphilis antibody, HBV, HCV virus quantification were all negative; ECOG activity status score: 0-2 points; Female subjects must have access to effective contraceptive measures (e.g., oral prescription contraceptives, injectable contraceptives, intrauterine devices, double blocking, contraceptive patches, male partner sterilizations) throughout the study period; Serum or urine pregnancy test results must be negative at screening and throughout the study; Willing to comply with the rules established in this protocol; Patients with relapsed/refractory CD19-positive acute B-cell leukemia (B-ALL, with the age of 1-60 years) or relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL, with the age of 5-65 years). Exclusion Criteria: Pregnant or lactating women; The following drugs or treatments should be excluded:High-dose glucocorticoids were used within 72h prior to UCAR-T infusion, except for physiological alternative therapies;Allogeneic cell therapies such as donor lymphocyte transfusion within 6 weeks prior to UCAR-T transfusion;GVHD treatment; Single extramedullary relapse B-ALL; Suffering from severe mental disorder; Active autoimmune diseases requiring immunotherapy; History of other malignant tumors; Patients with severe cardiovascular disease; Organ function is in the following abnormalities; Total bilirubin > 1.5 times the upper limit of normal unless the patient is Gilbert's syndrome; Partial thromboplastin time or activated partial thromboplastin time or international normalized ratio >1.5*ULN；in the absence of anticoagulant therapy; There is an active infectious disease or any major infectious event requiring high-level antibiotics; Any condition that, in the opinion of the investigator, may increase the subject's risk or interfere with the test results.

Ages Eligible for Study
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Minimum Age: 1 Year
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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD19-UCART<br>All patients will be treated with 1 injection of CD19-UCART. Three escalating dose-levels (1.0-2.0x10^6/kgBW, 2.5-5.0x10^6/kgBW, 5.5-10.0x10^6/kgBW) of CD19-UCART will be evaluated using a 3+3 design. Each CD19-UCART injection will be administered at Day 0. | Biological: CD19-UCART<br>* A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLTs) occurence | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 35 days after T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The total response rate after 90 days of treatment with study drug (overall response rate for ALL= CR+CRi; for NHL=CR+PR); | At 12 weeks, and overall | 
| Day 90 progression-free survival | The 90-day progression-free survival rate following drug therapy. | Assessed up to 3 months |