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

B-cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04289220
• Other study ID #: 2019-1-N-25318000002027
• Status: Recruiting
• Phase: Phase 1
• Start date: March 15, 2020
• Est. completion date: September 15, 2023

Study information

• Verified date: May 2021
• Source: Yan'an Affiliated Hospital of Kunming Medical University
• Contact: Zongliu Hou
• Phone: 86-0871-63211157
• Email: hzl579[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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-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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: September 15, 2023
• Est. primary completion date: March 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• B Cell Lymphoma
• B-cell Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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

Locations

Country	Name	City	State
China	Kunming Yan'an Hospital	Kunming	Yunnan

Sponsors (1)

Lead Sponsor	Collaborator
Yan'an Affiliated Hospital of Kunming Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grade 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.	14 day
Primary	Persistence of anti-CD19 CAR-T cells in participants	Copies numbers of CAR in peripheral blood (PB)	1 year
Secondary	Overall survival	For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason	3 years
Secondary	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.	3 years
Secondary	Duration of Response after administration	Duration of Response after administration	3 years