B-Cell LeukemiaPhase 1/2NCT03098355
Interleukin-2 Following 4SCAR19/22 T Cells Targeting Refractory and/or Recurrent B Cell Malignancies
A Phase 1/2 study testing 4SCAR19/22 T cells and Interleukin-2 in people with B-Cell Leukemia and B-Cell Lymphoma, run by Zhujiang Hospital at 1 site in China.
Trial summary
Clinical studies of CD19 CAR-T cells in the treatment of blood and lymphatic system tumors have achieved unprecedented successes. Because of the heterogeneity of the tumor, patients often carry CD19-negative tumor cell clones that express alternative target antigens (such as CD22, CD20 and CD123). Read more about this study
- Who is it for?
- Ages 1 year to 14 years
- Conditions the study is for
- B-Cell Leukemia, B-Cell Lymphoma
- What is being tested?
- 4SCAR19/22 T cells and Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteChina
- Study dates
- 30 Dec 2017to 31 Dec 2023
- Phase
- Phase 1/2
- 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 1 year to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Relapsed or refractory CD19+ B-cell lymphoma or leukemia.
- Measurable disease.
- Karnofsky/jansky score of 60% or greater.
- ≥1 years old and ≤14 years.
- Fertile females/males.
- Expected survival>12 weeks.
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- Histologically confirmed as CD19/20-positive ALL/NHL and who meet one of the following conditions:
- Patients receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR.
- Recurrent disease and not eligible for allogeneic stem cell transplantation, and stable disease after therapy but refused further treatment.
- Disease recurrence after stem cell transplantation.
- Diagnosis as lymphoma, and refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy.
- Creatinine < 2.5 mg/dl.
- Alanine transaminase (ALT) <3x upper limit of normal (ULN), aspartate aminotransferase (AST) <3x ULN.
- Bilirubin < 2.0 mg/dl.
- Adequate venous access for apheresis, and no other contraindications for leukapheresis.
- Take contraceptive measures before recruit to this trial.
- Written voluntary informed consent is given.
Who cannot join
- A history of mental illness and poorly controlled.
- Patients with symptoms of central nervous system.
- Suffering severe cardiovascular or respiratory disease.
- Accompanied by other malignant tumor.
- Known human immunodeficiency virus (HIV) infection.
- Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection).
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- Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient.
- Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration.
- Patients that do not consent to tissue and blood sample collection and storage in a biobank.
- Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed 48 hours before infusion.
- Pregnancy and nursing females.
Trial locations and contacts
1 site in 1 country.
China1 site
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, 510282
About this study
Official title: Anti-CD19/CD22 4th Generation CAR-T Cells (4SCAR19/22) Followed by Interleukin-2 Treating Pediatric Relapsed and Refractory B Cell Malignancies
Clinical studies of CD19 CAR-T cells in the treatment of blood and lymphatic system tumors have achieved unprecedented successes. Because of the heterogeneity of the tumor, patients often carry CD19-negative tumor cell clones that express alternative target antigens (such as CD22, CD20 and CD123). In order to effectively eradicate all tumor clones and prevent recurrence, alternative tumor antigens besides CD19 are considered for CAR-T cell targeting. In this tudy, autologous T cells are genetically modified with 4th generation anti-CD19 and anti-CD22 CARs (4SCAR19/22) using lentiviral vectors. For safety consideration, the 4SCAR is engineered with an inducible caspase 9 self-withdrawal genetic design that allows for rapid elimination of the infused CAR-T cells. Interleukin-2 has been shown to boost immune response against leukemia cells. The serum interleukin-6 level will be monitored and when it returns to normal range by day 28 after CAR-T cell infusion, patients will receive subcutaneous injection of interleukin-2, and evaluated for 24 months for safety, efficacy and persistence of CAR T cells.
Read the detailed description
Objectives:
- Primary Outcome Measures:
- Evaluate the frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) [ Time Frame: From date of dosing ( day 1 ) up to 50 weeks ]
- Evaluate grade 3 and higher toxicity rate of patients (toxicity possibly attributed to 4SCAR19/22 T cells)
- Evaluate the safety and effect of administration of 4SCAR19/22 T cells followed by interleukin-2 in treating pediatric patients with relapsed and refractory B cell malignancies.
- Secondary:
- Evaluate Overall Complete Remission Rate (ORR).
- Evaluate overall response rate including complete remission (CR) and complete remission with incomplete blood count recovery (CRi) .
- Evaluate duration of remission (DOR).
- To evaluate the incidence and the treatment effect of cytokine release syndrome (CRS).
- To determine the expansion and functional persistence of 4SCAR19/22 T cells in the peripheral blood of patients and the correlation with antitumor effects;
Design:
- In this single-center, open-label, nonrandomized, no control, prospective clinical trial, a total of 30 patients with resistant or refractory B cell acute lymphoblastic leukemia (ALL) or non-hodgkin's lymphoma (NHL) will be enrolled. Patients with ALL will be diagnosed according to bone marrow morphology, immunophenotype, cytogenetic and molecular examination. Patients with NHL will be diagnosed according to bone marrow morphology, biopsy pathology and imaging examination.
- Peripheral blood mononuclear cells (PBMC) will be obtained by apheresis, and T cells will be activated and modified to express the 4SCAR-CD19/22 gene.
- On Day -2 to -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR-CD19/22 lentiviral transduction. The total culture time is approximately 5-7 days.
- Patients will receive lymphodepleting chemotherapy composed of cyclophosphamide and fludarabine prior to cell infusion,
- Participants will receive the CAR-T cells at a total dose of 0.5-5x10^6/kg.
- Participants will receive regular subcutaneous injection of interleukin-2 of 250,000iu/m^2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months after their serum interleukin-6 levels returned to normal range from day 28 after CAR-T cell infusion.
- Patients will be monitored for toxicity including cytokine release syndrome, hematologic toxicities and B-cell aplasia, for response of their underlying malignancy and for CAR-T cell persistence in the blood, marrow and cerebral spinal fluid (CSF).
- Conditions
- B-Cell Leukemia, B-Cell Lymphoma
- Being tested
- 4SCAR19/22 T cells, Interleukin-2
- Keywords
- CART, CD19, CD22, Interleukin-2
- Medical subject headings
- Leukemia, B-Cell, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4SCAR19/22 T cellsBiological
CD19/CD22-targeted 4th Generation CAR-T Cell (4SCAR19/22)
Interleukin-2Drug
Also called IL-2
Interleukin-2 of 250,000iu/m^2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months.
| Study group | Role | What they receive |
|---|---|---|
| 4SCAR19/22 T cells and interleukin-2 | Experimental | Patients with resistant or refractory B cell acute lymphoblastic leukemia (ALL) or non-hodgkin's lymphoma (NHL) will receive CAR-T cells at a total dose of 0.5-5x10^6/kg and regular subcutaneous injection of interleukin-2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months after their serum interleukin-6 levels returned to normal range from day 28 after CAR-T cell infusion. Receives: Biological: 4SCAR19/22 T cells; Drug: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the frequency and severity of adverse events including, but not limited to, cytokine release syndrome (CRS)
b)Evaluate grade 3 and higher toxicity rate of patients (toxicity possibly attributed to 4SCAR19/22 T cells)
Measured: From date of dosing ( day 1 ) up to 50 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2017
- Study start30 Dec 2017
- Primary completion15 Dec 2022 (estimated)
- Study completion31 Dec 2023 (estimated)
Why it stopped: The company did not offer the appropriate CART services.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-Cell LeukemiaStudies of the same condition, open and under way.
- More trials run by Zhujiang HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zhujiang Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shenzhen Geno-Immune Medical Institute
- Responsible party
- Sponsor
- Investigators
- Li-hua Yang, Ph.D., Principal investigator, Southern Medical University, ChinaLung-Ji Chang, Ph.D., Study director, Shenzhen Geno-Immune Medical Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03098355
- Sponsor's protocol ID
- anti-CD19/22 CART Cells
- Status last verified
- Sep 2022
- First submitted
- 26 Mar 2017
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-CD19/CD22 4th Generation CAR-T Cells (4SCAR19/22) Followed by Interleukin-2 Treating Pediatric Relapsed and Refractory B Cell Malignancies
- ClinicalTrials.gov ID
- NCT03098355
- Acronym / sponsor ID
- anti-CD19/22 CART Cells
- Conditions
- B-Cell Leukemia, B-Cell Lymphoma
- Keywords
- CART, CD19, CD22, Interleukin-2
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The company did not offer the appropriate CART services.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Zhujiang HospitalUniversity, hospital or other
- Collaborators
- Shenzhen Geno-Immune Medical Institute
- Study start
- 30 Dec 2017 (actual)
- Primary completion
- 15 Dec 2022 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 31 Mar 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.
Clinical studies of CD19 CAR-T cells in the treatment of blood and lymphatic system tumors have achieved unprecedented successes. Because of the heterogeneity of the tumor, patients often carry CD19-negative tumor cell clones that express alternative target antigens (such as CD22, CD20 and CD123). In order to effectively eradicate all tumor clones and prevent recurrence, alternative tumor antigens besides CD19 are considered for CAR-T cell targeting. In this tudy, autologous T cells are genetically modified with 4th generation anti-CD19 and anti-CD22 CARs (4SCAR19/22) using lentiviral vectors. For safety consideration, the 4SCAR is engineered with an inducible caspase 9 self-withdrawal genetic design that allows for rapid elimination of the infused CAR-T cells. Interleukin-2 has been shown to boost immune response against leukemia cells. The serum interleukin-6 level will be monitored and when it returns to normal range by day 28 after CAR-T cell infusion, patients will receive subcutaneous injection of interleukin-2, and evaluated for 24 months for safety, efficacy and persistence of CAR T cells.
Detailed description
Objectives:
- Primary Outcome Measures:
- Evaluate the frequency and severity of adverse events, including, but not limited to, cytokine release syndrome (CRS) [ Time Frame: From date of dosing ( day 1 ) up to 50 weeks ]
- Evaluate grade 3 and higher toxicity rate of patients (toxicity possibly attributed to 4SCAR19/22 T cells)
- Evaluate the safety and effect of administration of 4SCAR19/22 T cells followed by interleukin-2 in treating pediatric patients with relapsed and refractory B cell malignancies.
- Secondary:
- Evaluate Overall Complete Remission Rate (ORR).
- Evaluate overall response rate including complete remission (CR) and complete remission with incomplete blood count recovery (CRi) .
- Evaluate duration of remission (DOR).
- To evaluate the incidence and the treatment effect of cytokine release syndrome (CRS).
- To determine the expansion and functional persistence of 4SCAR19/22 T cells in the peripheral blood of patients and the correlation with antitumor effects;
Design:
- In this single-center, open-label, nonrandomized, no control, prospective clinical trial, a total of 30 patients with resistant or refractory B cell acute lymphoblastic leukemia (ALL) or non-hodgkin's lymphoma (NHL) will be enrolled. Patients with ALL will be diagnosed according to bone marrow morphology, immunophenotype, cytogenetic and molecular examination. Patients with NHL will be diagnosed according to bone marrow morphology, biopsy pathology and imaging examination.
- Peripheral blood mononuclear cells (PBMC) will be obtained by apheresis, and T cells will be activated and modified to express the 4SCAR-CD19/22 gene.
- On Day -2 to -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR-CD19/22 lentiviral transduction. The total culture time is approximately 5-7 days.
- Patients will receive lymphodepleting chemotherapy composed of cyclophosphamide and fludarabine prior to cell infusion,
- Participants will receive the CAR-T cells at a total dose of 0.5-5x10^6/kg.
- Participants will receive regular subcutaneous injection of interleukin-2 of 250,000iu/m^2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months after their serum interleukin-6 levels returned to normal range from day 28 after CAR-T cell infusion.
- Patients will be monitored for toxicity including cytokine release syndrome, hematologic toxicities and B-cell aplasia, for response of their underlying malignancy and for CAR-T cell persistence in the blood, marrow and cerebral spinal fluid (CSF).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 4SCAR19/22 T cells and interleukin-2 | Experimental | Biological: 4SCAR19/22 T cells, Drug: Interleukin-2Patients with resistant or refractory B cell acute lymphoblastic leukemia (ALL) or non-hodgkin's lymphoma (NHL) will receive CAR-T cells at a total dose of 0.5-5x10^6/kg and regular subcutaneous injection of interleukin-2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months after their serum interleukin-6 levels returned to normal range from day 28 after CAR-T cell infusion. |
Who may qualify
- Ages
- 1 year to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (17 listed)
- Relapsed or refractory CD19+ B-cell lymphoma or leukemia.
- Measurable disease.
- Karnofsky/jansky score of 60% or greater.
- ≥1 years old and ≤14 years.
- Fertile females/males.
Key exclusion criteria (11 listed)
- A history of mental illness and poorly controlled.
- Patients with symptoms of central nervous system.
- Suffering severe cardiovascular or respiratory disease.
- Accompanied by other malignant tumor.
- Known human immunodeficiency virus (HIV) infection.
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 |
|---|---|---|
| 4SCAR19/22 T cellsCD19/CD22-targeted 4th Generation CAR-T Cell (4SCAR19/22) | Biological | 4SCAR19/22 T cells and interleukin-2 |
| Interleukin-2Also: IL-2Interleukin-2 of 250,000iu/m^2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months. | Drug | 4SCAR19/22 T cells and interleukin-2 |
Primary outcome
Evaluate the frequency and severity of adverse events including, but not limited to, cytokine release syndrome (CRS)
Time frame: From date of dosing ( day 1 ) up to 50 weeks
b)Evaluate grade 3 and higher toxicity rate of patients (toxicity possibly attributed to 4SCAR19/22 T cells)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
- Individual participant dataSharing planned: No
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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.
Li-hua Yang, Ph.D. principal investigator
Southern Medical University, China
Lung-Ji Chang, Ph.D. study director
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 Phase 1/2 study testing 4SCAR19/22 T cells and Interleukin-2 in people with B-Cell Leukemia and B-Cell Lymphoma, run by Zhujiang Hospital 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 17 inclusion and 11 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: withdrawn, as of the sponsor's last update on 18 Mar 2024. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Evaluate the frequency and severity of adverse events including, but not limited to, cytokine release syndrome (CRS) (time frame: From date of dosing ( day 1 ) up to 50 weeks). 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 18 Mar 2024; AzTrials last refreshed its copy on 6 Nov 2026.