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

Last updated: May 12, 2021
Sponsor: Yan'an Affiliated Hospital of Kunming Medical University
Overall Status: Active - Recruiting

Phase

1

Condition

Lymphoma, B-cell

Leukemia

Lymphocytic Leukemia, Acute

Treatment

N/A

Clinical Study ID

NCT04289220
2019-1-N-25318000002027
  • Ages 18-70
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Patients or their legal guardians voluntarily participate and sign the InformedConsent Document;
  2. Male or female patients aged 18 to 70 years (inclusive);
  3. Pathologically and histologically confirmed CD19 + B cell tumors; Patients currentlyhave no effective treatment options, such as chemotherapy or relapse afterhematopoietic stem cell transplantation; Or patients voluntarily choose transfusion ofanti-CD19 CAR-T cells as the first treatment program;
  4. B-cell tumors / lymphomas and B-cell acute lymphoblastic leukemia include thefollowing four types:1) B-cell acute lymphoblastic leukemia;2) Indolent B-celllymphomas;3) Aggressive B-cell lymphoma; 4) Multiple myeloma;
  5. Subjects:

(1) Residual lesions remain after treatment and Not suitable for Hematopoietic stem celltransplantation (auto/allo-HSCT); (2) Relapse after Complement receptor 1 (CR1) andunsuitable for HSCT; (3) Patients with high risk factors; (4) Relapse or no remission afterhematopoietic stem cell transplantation or cell immunotherapy. 6. Have measurable or evaluable tumor foci; 7. Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Serum glutamic pyruvic transaminase (ALT) and serum glutamic oxaloacetic transaminase (AST) <3 ×upper limit of normal (ULN);2) Total bilirubin ≤34.2μmol/L;3) Serumcreatinine<220μmol/L;4) Baseline oxygen saturation≥95%;5) Left ventricular ejectionfraction（LVEF）≥40%.
  1. Subjects who did not receive Chemotherapy, Radiotherapy, Immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; Relevanttoxicity≤1 grade before enrollment (except for low toxicity such as hair loss);
  2. Peripheral superficial venous blood flow is smooth, which can meet the needs ofintravenous drip;
  3. Clinical performance status of eastern cancer cooperation group (ECOG) score ≤2,Expected survival≥3 months;

Exclusion

Exclusion Criteria:

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

Study Design

Total Participants: 10
Study Start date:
March 15, 2020
Estimated Completion Date:
September 15, 2023

Study 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-α, 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.

Connect with a study center

  • Kunming Yan'an Hospital

    Kunming, Yunnan 650000
    China

    Active - Recruiting

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