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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
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
Kunming Yan'an Hospital
Kunming, Yunnan, China
RECRUITINGGrade and number of cytokine release syndrome and neurotoxic effects in participants receiving treatment
Anti-CD19 CAR-T cells growing use requires further education/training and prompt management of safety and tolerability.
Time frame: 14 day
Persistence of anti-CD19 CAR-T cells in participants
Copies numbers of CAR in peripheral blood (PB)
Time frame: 1 year
Overall survival
For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason
Time frame: 3 years
Progress Free Survival
Progression-free survival refers to the period between the start of treatment for participants and the observation of disease progression or death for any reason.
Time frame: 3 years
Duration of Response after administration
Duration of Response after administration
Time frame: 3 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.