B Cell LymphomaPhase 1NCT04289220
Anti-CD19 CAR in PiggyBac Transposon-Engineered T Cells for Relapsed/Refractory B-cell Lymphoma or B-cell Acute Lymphoblastic Leukemia
A Phase 1 study testing Anti-CD19 CAR-T Cells Injection in people with B Cell Lymphoma and B-cell Acute Lymphoblastic Leukemia, run by Yan'an Affiliated Hospital of Kunming Medical University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- B Cell Lymphoma, B-cell Acute Lymphoblastic Leukemia
- What is being tested?
- Anti-CD19 CAR-T Cells Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 15 Mar 2020to 15 Sep 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
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- 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;
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Kunming Yan'an Hospital
Kunming, Yunnan, 650000
Lin Li, aileenali@163.com
About this study
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
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.
Read the 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.
- Being tested
- Anti-CD19 CAR-T Cells Injection
- Medical subject headings
- Lymphoma, B-Cell, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD19 CAR-T Cells InjectionBiological
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
| Study group | Role | What they receive |
|---|---|---|
| Anti-CD19 CAR-T Cells Injection | Experimental | 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 Receives: Biological: Anti-CD19 CAR-T Cells Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 day
Persistence of anti-CD19 CAR-T cells in participants
Copies numbers of CAR in peripheral blood (PB)
Measured: 1 year
Secondary outcomes (3)
Overall survival
For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason
Measured: 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.
Measured: 3 years
Duration of Response after administration
Duration of Response after administration
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2020
- Study start15 Mar 2020
- Primary completion15 Mar 2023 (estimated)
- Study completion15 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yan'an Affiliated Hospital of Kunming Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zongliu Hou, Study director, Kunming Yan'an Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04289220
- Sponsor's protocol ID
- 2019-1-N-25318000002027
- Status last verified
- May 2021
- First submitted
- 26 Feb 2020
- Last updated
- 13 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04289220
- Acronym / sponsor ID
- 2019-1-N-25318000002027
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Yan'an Affiliated Hospital of Kunming Medical UniversityUniversity, hospital or other
- Study start
- 15 Mar 2020 (actual)
- Primary completion
- 15 Mar 2023 (estimated)
- Study completion
- 15 Sep 2023 (estimated)
- First posted
- 28 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-CD19 CAR-T Cells Injection | Experimental | Biological: Anti-CD19 CAR-T Cells InjectionAnti-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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-CD19 CAR-T Cells InjectionDosage 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 | Biological | Anti-CD19 CAR-T Cells Injection |
Primary outcome
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.
Persistence of anti-CD19 CAR-T cells in participants
Time frame: 1 year
Copies numbers of CAR in peripheral blood (PB)
3 secondary outcomes
Overall survival
Time frame: 3 years
Progress Free Survival
Time frame: 3 years
Duration of Response after administration
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zongliu Hou study director
Kunming Yan'an Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anti-CD19 CAR-T Cells Injection in people with B Cell Lymphoma and B-cell Acute Lymphoblastic Leukemia, run by Yan'an Affiliated Hospital of Kunming Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zongliu Hou (86-0871-63211157, hzl579@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Grade and number of cytokine release syndrome and neurotoxic effects in participants receiving treatment (time frame: 14 day). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2021.