Safety and Efficacy Evaluation of CD19-UCART

Acute Lymphoblastic Leukemia (ALL) Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03229876
• Other study ID #: 2018CAR-00CH1
• Status: Suspended
• Phase: N/A
• Start date: June 1, 2019
• Est. completion date: December 30, 2023

Study information

• Verified date: March 2023
• Source: Bioray Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 20
• Est. completion date: December 30, 2023
• Est. primary completion date: December 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia (ALL)
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma (NHL)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
China	First Affliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	First Affliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (4)

Lead Sponsor	Collaborator
Bioray Laboratories	First Affiliated Hospital of Zhejiang University, Second Xiangya Hospital of Central South University, The First Affiliated Hospital of Zhengzhou University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Progrssion-free survival	The time from treatment with study drug to tumor progression or death.	up to 2 years after infusion
Other	Overall survival	the time from treatment with study drug to death by any cause.	up to 2 years after infusion
Primary	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	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
Secondary	Day 90 progression-free survival	The 90-day progression-free survival rate following drug therapy.	Assessed up to 3 months