Anti-CD19 CAR in PiggyBac Transposon-Engineered T Cells for Relapsed/Refractory B-cell Lymphoma or B-cell Acute Lymphoblastic Leukemia

  • STATUS
    Recruiting
  • End date
    Sep 15, 2023
  • participants needed
    10
  • sponsor
    Yan'an Affiliated Hospital of Kunming Medical University
Updated on 22 May 2021
cancer
remission
multiple myeloma
cell transplantation
leukemia
lymphocytic leukemia
b-cell acute lymphoblastic leukemia
cancer chemotherapy
b-cell lymphoma

Summary

Our previous study demonstrated that anti-CD19 chimeric antigen receptor in piggyBac transposon-engineered T cells have strong tumor-killing activity in vitro and therapeutic effects in cell line-derived xenograft models, and no obvious side effects such as neurotoxicity and cytokine storm occurred. Therefore, we want to evaluate the safety and clinical effect of anti-CD19 CAR-T cells in clinical trials.

Description

Using piggyBac transposon/transposase system to deliver genes into primary human T cells - example expression of CD19 CAR.CARs specific to the human CD19 antigen were used. All CARs contained the scFv against human CD19 (clone FMC-63), The third BBz CD28z CAR consisted of the scFv linked to the intracellular domains of CD28, 4-1BB and CD3z through a CD28 transmembrane domain;

Subjects with relapsed/refractory CD19-positive B-cell Lymphoma or B-ALL can participate if all eligibility criteria are met. All patients received chemotherapy with fludarabine and cyclophosphamide before the infusion of anti-CD19 CAR-T cells.. After the infusion, subjects will accept follow-up for side effects and effect of anti-CD19 CAR-T cells.

Follow-up :

Safety and adverse events (safety and tolerability of anti-CD19 CAR-T cell therapy within 14 days): The number and severity of adverse events, an evaluation of their association with the anti-CD19 CAR-T cell treatment, and the outcome of the adverse events. Possible adverse events include cytokine release syndrome, hypotension, reversible neurotoxicity, hypogammaglobulinemia, etc. CT was used to evaluate B-lymphoma lesions. B-ALL bone marrow samples were collected by bone marrow aspiration to assess minimal residual disease. Flow cytometry was used to detect proportion of T cells, B cells, and NK cells in the blood, and expression of CD3, CD4, CD8, anti-CD19 CAR to determine the effect of anti-CD19 CAR-T treatment. Plasma levels of the cytokines IFN-gamma, TNF-, IL-2, GM-CSF, IL-10, and IL-6 were also determined.

Data analysis:

Overall survival and progress free survival were determined by the Kaplan-Meier method, using all enrolled patients to determine overall survival.

Study procedures may be performed while hospitalized.

Details
Condition Lymphoma, Non-Hodgkin's Lymphoma, b cell lymphomas, B-Cell Lymphoma, Lymphoma, B-Cell, b-cell lymphomas, b cell lymphoma, B-cell Acute Lymphoblastic Leukemia
Treatment Anti-CD19 CAR-T Cells Injection
Clinical Study IdentifierNCT04289220
SponsorYan'an Affiliated Hospital of Kunming Medical University
Last Modified on22 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients or their legal guardians voluntarily participate and sign the Informed Consent Document
Male or female patients aged 18 to 70 years (inclusive)
Pathologically and histologically confirmed CD19 + B cell tumors; Patients currently have no effective treatment options, such as chemotherapy or relapse after hematopoietic stem cell transplantation; Or patients voluntarily choose transfusion of anti-CD19 CAR-T cells as the first treatment program
B-cell tumors / lymphomas and B-cell acute lymphoblastic leukemia include the following four types:1) B-cell acute lymphoblastic leukemia;2) Indolent B-cell lymphomas;3) Aggressive B-cell lymphoma; 4) Multiple myeloma
Subjects
(1) Residual lesions remain after treatment and Not suitable for Hematopoietic
stem cell transplantation (auto/allo-HSCT); (2) Relapse after Complement
receptor 1 (CR1) and unsuitable for HSCT; (3) Patients with high risk factors
(4) Relapse or no remission after hematopoietic stem cell transplantation or
cell immunotherapy
\. Have measurable or evaluable tumor foci
\. Liver, kidney and cardiopulmonary functions meet the following
requirements
Serum glutamic pyruvic transaminase (ALT) and serum glutamic oxaloacetic transaminase (AST) <3 upper limit of normal (ULN);2) Total bilirubin 34.2mol/L;3) Serum creatinine<220mol/L;4) Baseline oxygen saturation95%;5) Left ventricular ejection fractionLVEF40%
Subjects who did not receive Chemotherapy, Radiotherapy, Immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; Relevant toxicity1 grade before enrollment (except for low toxicity such as hair loss)
Peripheral superficial venous blood flow is smooth, which can meet the needs of intravenous drip
Clinical performance status of eastern cancer cooperation group (ECOG) score 2,Expected survival3 months

Exclusion Criteria

Pregnant (urine/blood pregnancy test positive) or lactating women
Planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion
Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment
Active or uncontrollable infection within four weeks prior to enrollment
Patients with active hepatitis B/C
HIV-infected patients
Severe autoimmune or immunodeficiency disorders
Patients are allergic to macromolecule drugs such as antigens or cytokines
Subjects participated in other clinical trials within 6 weeks before enrollment
Systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones)
Mental illness
Drug abuse/addiction
The investigators consider other conditions unsuitable for enrollment
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