Safety and Efficacy Evaluation of CD19-UCART

NCT03229876 | Suspended

• 1 other identifier: 2018CAR-00CH1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Lymphoblastic Leukemia (ALL); Non Hodgkin Lymphoma (NHL)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Objective Response Rate

  At 12 weeks, and overall

• Day 90 progression-free survival

  Assessed up to 3 months

Other Outcomes (3)

• UCART cell survival time

  up to 1 year after infusion

• Progrssion-free survival

  up to 2 years after infusion

• Overall survival

  up to 2 years after infusion

Study Arms (1)

CD19-UCART

EXPERIMENTAL

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

Interventions

CD19-UCART BIOLOGICAL

A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.

CD19-UCART

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bioray Laboratories: lead
• The First Affiliated Hospital of Zhengzhou University: collaborator
• First Affiliated Hospital of Zhejiang University: collaborator
• Second Xiangya Hospital of Central South University: collaborator

Study Sites (2)

First Affliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

First Affliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma

Study Officials

• Yi Zhang, Professor

  First Affliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

• He Huang, Professor

  First Affliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: July 26, 2017
• Study Start: June 1, 2019
• Primary Completion: December 15, 2023
• Study Completion: December 30, 2023
• Last Updated: July 24, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)