Clinical trial NCT03229876: Safety and Efficacy Evaluation of CD19-UCART
Official title: 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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Acute Lymphoblastic Leukemia (ALL)
Non Hodgkin Lymphoma (NHL)
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Zhengzhou University
name: First Affiliated Hospital of Zhejiang University
name: Second Xiangya Hospital of Central South University
First posted: 2017-07-26
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Voluntarily participating in this clinical study and signing the informed consent form; The estimated survival period is at least one month;
2. No other serious cardiopulmonary diseases, and normal liver and kidney functions (except for subjects with tumor lesions in their liver and kidneys);
3. 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;
4. 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);
5. 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;
6. 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;
7. Cardiac function: Good hemodynamic stability, and the left ventricular ejection fraction (LVEF) ≥ 55%;
8. Serum viral EBV-DNA, CMV-DNA, HIV antibody and syphilis antibody, HBV, HCV virus quantification were all negative;
9. ECOG activity status score: 0-2 points;
10. 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;
11. Willing to comply with the rules established in this protocol;
12. 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:

1. Pregnant or lactating women;
2. 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;
3. Single extramedullary relapse B-ALL;
4. Suffering from severe mental disorder;
5. Active autoimmune diseases requiring immunotherapy;
6. History of other malignant tumors;
7. Patients with severe cardiovascular disease;
8. Organ function is in the following abnormalities;
9. Total bilirubin \> 1.5 times the upper limit of normal unless the patient is Gilbert's syndrome;
10. Partial thromboplastin time or activated partial thromboplastin time or international normalized ratio \>1.5\*ULN；in the absence of anticoagulant therapy;
11. There is an active infectious disease or any major infectious event requiring high-level antibiotics;
12. Any condition that, in the opinion of the investigator, may increase the subject's risk or interfere with the test results.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs) occurence
timeFrame: Baseline up to 35 days after T cell infusion
Secondary outcomes:
measure: Objective Response Rate
timeFrame: At 12 weeks, and overall
measure: Day 90 progression-free survival
timeFrame: Assessed up to 3 months
Other outcomes:
measure: UCART cell survival time
timeFrame: up to 1 year after infusion
measure: Progrssion-free survival
timeFrame: up to 2 years after infusion
measure: Overall survival
timeFrame: up to 2 years after infusion
Locations:
city: Zhengzhou
country: China
facility: First Affliated Hospital of Zhengzhou University
state: Henan
city: Hangzhou
country: China
facility: First Affliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: First Affliated Hospital of Zhengzhou University
name: Yi Zhang, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affliated Hospital of Zhejiang University
name: He Huang, Professor
role: PRINCIPAL_INVESTIGATOR
References: