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

Primary Purpose

B Cell Lymphoma, B-cell Acute Lymphoblastic Leukemia

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Anti-CD19 CAR-T Cells Injection

About this trial

This is an interventional treatment trial for B Cell Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients or their legal guardians voluntarily participate and sign the Informed Consent Document;
Male or female patients aged 18 to 70 years (inclusive);
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;
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;
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:

Pregnant (urine/blood pregnancy test positive) or lactating women;
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;
Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment;
Active or uncontrollable infection within four weeks prior to enrollment;
Patients with active hepatitis B/C;
HIV-infected patients;
Severe autoimmune or immunodeficiency disorders;
Patients are allergic to macromolecule drugs such as antigens or cytokines;
Subjects participated in other clinical trials within 6 weeks before enrollment;
Systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);
Mental illness;
Drug abuse/addiction;
The investigators consider other conditions unsuitable for enrollment.

Sites / Locations

Kunming Yan'an HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Anti-CD19 CAR-T Cells Injection

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Persistence of anti-CD19 CAR-T cells in participants

Copies numbers of CAR in peripheral blood (PB)

Secondary Outcome Measures

Overall survival

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

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

Full Information

NCT ID

NCT04289220

First Posted

February 26, 2020

Last Updated

May 12, 2021

Sponsor

Yan'an Affiliated Hospital of Kunming Medical University

1. Study Identification

Unique Protocol Identification Number

NCT04289220

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Unknown status

Study Start Date

March 15, 2020 (Actual)

Primary Completion Date

March 15, 2023 (Anticipated)

Study Completion Date

September 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yan'an Affiliated Hospital of Kunming Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B Cell Lymphoma, B-cell Acute Lymphoblastic Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Anti-CD19 CAR-T Cells Injection

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Anti-CD19 CAR-T Cells Injection

Intervention Description

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

Primary Outcome Measure Information:

Title

Grade and number of cytokine release syndrome and neurotoxic effects in participants receiving treatment

Description

Anti-CD19 CAR-T cells growing use requires further education/training and prompt management of safety and tolerability.

Time Frame

14 day

Title

Persistence of anti-CD19 CAR-T cells in participants

Description

Copies numbers of CAR in peripheral blood (PB)

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Overall survival

Description

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

Title

Progress Free Survival

Description

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

Title

Duration of Response after administration

Description

Duration of Response after administration

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients or their legal guardians voluntarily participate and sign the Informed Consent Document; Male or female patients aged 18 to 70 years (inclusive); 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; 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; 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: Pregnant (urine/blood pregnancy test positive) or lactating women; 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; Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment; Active or uncontrollable infection within four weeks prior to enrollment; Patients with active hepatitis B/C; HIV-infected patients; Severe autoimmune or immunodeficiency disorders; Patients are allergic to macromolecule drugs such as antigens or cytokines; Subjects participated in other clinical trials within 6 weeks before enrollment; Systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones); Mental illness; Drug abuse/addiction; The investigators consider other conditions unsuitable for enrollment.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zongliu Hou

Phone

86-0871-63211157

hzl579@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zongliu Hou

Organizational Affiliation

Kunming Yan'an Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Kunming Yan'an Hospital

City

Kunming

State/Province

Yunnan

ZIP/Postal Code

650000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lin Li

aileenali@163.com

12. IPD Sharing Statement

Learn more about this trial

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

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