B-cell Acute Lymphoblastic Leukemia, B Cell Lymphoma
Conditions
Brief 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.
Interventions
BIOLOGICALAnti-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
Sponsors
Yan'an Affiliated Hospital of Kunming Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Patients or their legal guardians voluntarily participate and sign the Informed Consent Document; 2. Male or female patients aged 18 to 70 years (inclusive); 3. 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; 4. 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; 5. 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. 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) Serum creatinine\<220μmol/L;4) Baseline oxygen saturation≥95%;5) Left ventricular ejection fraction（LVEF）≥40%. 8\. Subjects who did not receive Chemotherapy, Radiotherapy, Immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; Relevant toxicity≤1 grade before enrollment (except for low toxicity such as hair loss); 9\. Peripheral superficial venous blood flow is smooth, which can meet the needs of intravenous drip; 10\. Clinical performance status of eastern cancer cooperation group (ECOG) score ≤2,Expected survival≥3 months;
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 subject whose 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 inhaled hormones); 11. Mental illness; 12. Drug abuse/addiction; 13. The investigators consider other conditions unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grade and number of cytokine release syndrome and neurotoxic effects in participants receiving treatment | 14 day | Anti-CD19 CAR-T cells growing use requires further education/training and prompt management of safety and tolerability. |
| Persistence of anti-CD19 CAR-T cells in participants | 1 year | Copies numbers of CAR in peripheral blood (PB) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 3 years | For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason |
| Progress Free Survival | 3 years | 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. |
| Duration of Response after administration | 3 years | Duration of Response after administration |
Countries
China
Contacts
Primary ContactZongliu Hou
Outcome results
None listed