NCT04289220

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

A Phase I Clinical Trial of Anti-CD19 Chimeric Antigen Receptor in PiggyBac Transposon-Engineered T Cells for the Treatment of Patients With Relapsed/Refractory/High-risk B-cell Lymphoma or B-cell Acute Lymphoblastic Leukemia

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Yan'an Affiliated Hospital of Kunming Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• B Cell Lymphoma
• B-cell Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Anti-CD19 CAR-T Cells Injection	Dosage form：injection Dosage:1-2.5x10\^6 cells/kg, 100ml/time, The CAR-T cells will be administered by i.v. injection over 20-30 minutes, Frequency: total one time

Timeline

• Start date: 2020-03-15
• Primary completion: 2023-03-15
• Completion: 2023-09-15
• First posted: 2020-02-28
• Last updated: 2021-05-13

Locations

1 site across 1 country: China