Safety and Efficacy Evaluation of CD19-UCART

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

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.

Study Overview

• Status: Suspended
• Conditions: Acute Lymphoblastic Leukemia (ALL); Non Hodgkin Lymphoma (NHL)
• Intervention / Treatment: Biological: CD19-UCART

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • First Affliated Hospital of Zhengzhou University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • First Affliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD19-UCART; 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; A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
UCART cell survival time	The number of UCART cells surviving in the body within 90 days after receiving the study drug;	up to 1 year after infusion
Progrssion-free survival	The time from treatment with study drug to tumor progression or death.	up to 2 years after infusion
Overall survival	the time from treatment with study drug to death by any cause.	up to 2 years after infusion

Collaborators and Investigators

• Sponsor: Bioray Laboratories
• Collaborators: First Affiliated Hospital of Zhejiang University; The First Affiliated Hospital of Zhengzhou University; Second Xiangya Hospital of Central South University
• Investigators: Principal Investigator: Yi Zhang, Professor, First Affliated Hospital of Zhengzhou University; Principal Investigator: He Huang, Professor, First Affliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Estimated): December 15, 2023
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: July 19, 2017
• First Submitted That Met QC Criteria: July 23, 2017
• First Posted (Actual): July 26, 2017

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Lymphoma; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 2018CAR-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No