B-cell MalignanciesNCT03050190
A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies
A study testing Therapeutic 4SCAR19 cells in people with B-cell Malignancies, run by Shenzhen Geno-Immune Medical Institute at 1 site in China.
Trial summary
The study will evaluate safety and efficacy of a 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- B-cell Malignancies
- What is being tested?
- Therapeutic 4SCAR19 cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2025to 31 Jul 2026
- Phase
- Interventional
- 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- aged more than 6 months.
- malignant B cell surface expression CD19 molecules.
- the KPS score over 80 points, and survival time is more than 3 months.
- greater Hgb 80 g/L.
- no contraindications to solid and cell separation
Who cannot join
- accompanied with other active diseases, the treatment is difficult to correct.
- bacteria, fungus, or virus infection, unable to control.
- people living with HIV.
- active HBV and HCV infection.
- of pregnancy and nursing mothers.
- before entering the test of the use of glucocorticoid systemic treatment within a week.
- confirmed before used CAR - but invalid
Trial locations and contacts
1 site in 1 country.
About this study
The study will evaluate safety and efficacy of a 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.
Read the detailed description
Background:
T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. Recent successes suggest that increased costimulatory signaling in the CAR design is critical for long term efficacy. Activation of T cell response from large tumor burden may induce a severe response. To increase safety, a novel design using an inducible caspase 9 fusion gene has been incorporated in the CAR gene. A 4th generation CAR lentiviral vector (4SCAR) carrying T cell costimulatory signals for CD28/CD27 plus an inducible apoptotic caspase 9 gene has been established. The study aims to evaluate the activities of a new CAR gene-modified T cells targeting CD19-positive tumors based on a CD19-specific single chain gene constructed 4SCAR (4SCAR19).
Objective:
To evaluate safety and efficacy of administrating 4SCAR19 T cells to patients with CD19 positive B cell malignancies following a cyclophosphamide/fludarabine based conditioning regimen.
Eligibility:
Patients older than 6-month-old with CD19 positive B cells malignancies that have recurred after or refractory to standard therapy and is deemed incurable using standard treatment.
Design:
Participants will be screened based on cancer cell phenotype analyzed using flow cytometry or immunohistochemical staining methods.
Peripheral blood mononuclear cells (PBMC) will be obtained through apheresis, and T cells will be activated and modified to express the 4SCAR19 gene.
On Day -5 to -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR19 lentiviral transduction. The total cell preparation time is approximately 5-7 days.
Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accommodate the modified CAR T cells. The preparative regimen will be based on patient immune condition and consistent with standard chemotherapy conditioning regimen.
Participants will receive an infusion of the modified 4SCAR19 T cells and closely followed up for treatment-related responses.
Participants will be continuously monitored for CAR T cells and clinical responses at present timeline.
- Conditions
- B-cell Malignancies
- Being tested
- Therapeutic 4SCAR19 cells
- Keywords
- CART therapy, 4SCAR19, CD19, B cell leukemia, B-ALL
- Medical subject headings
- Leukemia, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Therapeutic 4SCAR19 cellsGenetic
Autologous 4th generation withdrawal lentiviral-transduced 4S CAR-T19
| Study group | Role | What they receive |
|---|---|---|
| Therapeutic 4SCAR19 cells | Experimental | Patients who have relapsed and refractory B cell leukemia after chemotherapy will be treated prophylactically with CD19-specific gene-engineered T cells. Receives: Genetic: Therapeutic 4SCAR19 cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events
physiological parameter (for safety, measuring cytokine response, fever, symptoms)
Measured: 24 weeks
Secondary outcomes (1)
Anti tumor activity of fourth generation anti CD19 CAR-T cells in patients with relapsed or refractory B cell malignancies
scale of CAR copies and leukemic cell burden (for efficacy)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2017
- Study start1 May 2025
- Primary completion1 Jul 2026
- Study completion31 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B-cell MalignanciesStudies of the same condition, open and under way.
- More trials run by Shenzhen Geno-Immune Medical InstituteThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shenzhen Geno-Immune Medical Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
- Investigators
- Lung-Ji Chang, Principal investigator, Shenzhen Geno-Immune Medical Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03050190
- Sponsor's protocol ID
- GIMI-IRB-16001
- Status last verified
- Oct 2026
- First submitted
- 8 Feb 2017
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Nair S, Wang JB, Tsao ST, Liu Y, Zhu W, Slayton WB, Moreb JS, Dong L, Chang LJ. Functional Improvement of Chimeric Antigen Receptor Through Intrinsic Interleukin-15Ralpha Signaling. Curr Gene Ther. 2019;19(1):40-53. doi: 10.2174/1566523218666181116093857.
PubMed 30444200
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies
- ClinicalTrials.gov ID
- NCT03050190
- Acronym / sponsor ID
- GIMI-IRB-16001
- Conditions
- B-cell Malignancies
- Keywords
- CART therapy, 4SCAR19, CD19, B cell leukemia, B-ALL
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Shenzhen Geno-Immune Medical InstituteUniversity, hospital or other
- Study start
- 1 May 2025 (actual)
- Primary completion
- 1 Jul 2026 (actual)
- Study completion
- 31 Jul 2026 (actual)
- First posted
- 10 Feb 2017 (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.
The study will evaluate safety and efficacy of a 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) for patients with B cell malignancies. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.
Detailed description
Background:
T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. Recent successes suggest that increased costimulatory signaling in the CAR design is critical for long term efficacy. Activation of T cell response from large tumor burden may induce a severe response. To increase safety, a novel design using an inducible caspase 9 fusion gene has been incorporated in the CAR gene. A 4th generation CAR lentiviral vector (4SCAR) carrying T cell costimulatory signals for CD28/CD27 plus an inducible apoptotic caspase 9 gene has been established. The study aims to evaluate the activities of a new CAR gene-modified T cells targeting CD19-positive tumors based on a CD19-specific single chain gene constructed 4SCAR (4SCAR19).
Objective:
To evaluate safety and efficacy of administrating 4SCAR19 T cells to patients with CD19 positive B cell malignancies following a cyclophosphamide/fludarabine based conditioning regimen.
Eligibility:
Patients older than 6-month-old with CD19 positive B cells malignancies that have recurred after or refractory to standard therapy and is deemed incurable using standard treatment.
Design:
Participants will be screened based on cancer cell phenotype analyzed using flow cytometry or immunohistochemical staining methods.
Peripheral blood mononuclear cells (PBMC) will be obtained through apheresis, and T cells will be activated and modified to express the 4SCAR19 gene.
On Day -5 to -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR19 lentiviral transduction. The total cell preparation time is approximately 5-7 days.
Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accommodate the modified CAR T cells. The preparative regimen will be based on patient immune condition and consistent with standard chemotherapy conditioning regimen.
Participants will receive an infusion of the modified 4SCAR19 T cells and closely followed up for treatment-related responses.
Participants will be continuously monitored for CAR T cells and clinical responses at present timeline.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Therapeutic 4SCAR19 cells | Experimental | Genetic: Therapeutic 4SCAR19 cellsPatients who have relapsed and refractory B cell leukemia after chemotherapy will be treated prophylactically with CD19-specific gene-engineered T cells. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- aged more than 6 months.
- malignant B cell surface expression CD19 molecules.
- the KPS score over 80 points, and survival time is more than 3 months.
- greater Hgb 80 g/L.
- no contraindications to solid and cell separation
Key exclusion criteria (7 listed)
- accompanied with other active diseases, the treatment is difficult to correct.
- bacteria, fungus, or virus infection, unable to control.
- people living with HIV.
- active HBV and HCV infection.
- of pregnancy and nursing mothers.
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 |
|---|---|---|
| Therapeutic 4SCAR19 cellsAutologous 4th generation withdrawal lentiviral-transduced 4S CAR-T19 | Genetic | Therapeutic 4SCAR19 cells |
Primary outcome
Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events
Time frame: 24 weeks
physiological parameter (for safety, measuring cytokine response, fever, symptoms)
1 secondary outcome
Anti tumor activity of fourth generation anti CD19 CAR-T cells in patients with relapsed or refractory B cell malignancies
Time frame: 1 year
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Derived from this study: PubMed 30444200Nair S, Wang JB, Tsao ST, Liu Y, Zhu W, Slayton WB, Moreb JS, Dong L, Chang LJ. Functional Improvement of Chimeric Antigen Receptor Through Intrinsic Interleukin-15Ralpha Signaling. Curr Gene Ther. 2019;19(1):40-53. doi: 10.2174/1566523218666181116093857.
- Individual participant dataSharing planned: Undecided
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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.
Lung-Ji Chang principal investigator
Shenzhen Geno-Immune Medical Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Therapeutic 4SCAR19 cells in people with B-cell Malignancies, run by Shenzhen Geno-Immune Medical Institute 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 5 inclusion and 7 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: stopped early, as of the sponsor's last update on 30 Oct 2026. 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.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03050190, which also lists 1 linked publication.
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 30 Oct 2026.