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

May 12, 2021 updated by: Yan'an Affiliated Hospital of Kunming Medical University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Zongliu Hou
  • Phone Number: 86-0871-63211157
  • Email: hzl579@163.com

Study Locations

  • China
    • Yunnan
      • Kunming, Yunnan, China, 650000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anti-CD19 CAR-T Cells Injection
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Grade and number of cytokine release syndrome and neurotoxic effects in participants receiving treatment
Time Frame: 14 day
Anti-CD19 CAR-T cells growing use requires further education/training and prompt management of safety and tolerability.
14 day
Persistence of anti-CD19 CAR-T cells in participants
Time Frame: 1 year
Copies numbers of CAR in peripheral blood (PB)
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 3 years
For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason
3 years
Progress Free Survival
Time Frame: 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.
3 years
Duration of Response after administration
Time Frame: 3 years
Duration of Response after administration
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yan'an Affiliated Hospital of Kunming Medical University

Investigators

  • Study Director: Zongliu Hou, Kunming Yan'an Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2020

Primary Completion (Anticipated)

March 15, 2023

Study Completion (Anticipated)

September 15, 2023

Study Registration Dates

First Submitted

February 26, 2020

First Submitted That Met QC Criteria

February 26, 2020

First Posted (Actual)

February 28, 2020

Study Record Updates

Last Update Posted (Actual)

May 13, 2021

Last Update Submitted That Met QC Criteria

May 12, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-1-N-25318000002027

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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