B-cell Non-Hodgkin's LymphomaPhase 1NCT05453669
Clinical Study of the Efficacy of CD19-CAR-DNT Cells in the Treatment of Relapsed/Refractory B-cell NHL
A Phase 1 study testing CD19-CAR-DNT cells in people with B-cell Non-Hodgkin's Lymphoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
To evaluate the safety and tolerability of CD19-CAR-DNT cells infusion in subjects with relapsed/refractory B-cell non-Hodgkin's Lymphoma Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- B-cell Non-Hodgkin's Lymphoma
- What is being tested?
- CD19-CAR-DNT cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 15 Jun 2022to Jun 2025
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily sign an ICF and expect to complete the study procedures for follow-up examinations and treatment.
- Aged 18 to 75 years (including cut-offs), regardless of gender
- A diagnosis of B-cell non-Hodgkin's lymphoma confirmed by cytology or pathological histology according to WHO 2016 criteria, including pathologically confirmed diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL) and high-grade B-cell lymphoma (HGBCL).
- Relapsed/refractory B-cell non-Hodgkin's lymphoma, provided one of the following conditions is met:
- Subjects with B-cell non-Hodgkin's lymphoma who have failed at least second-line regimens (including relapse, non-remission, progression) and have received a standardised regimen of anti-CD20 monoclonal antibodies (except CD20-negative) and anthracyclines;
- Relapse after autologous haematopoietic stem cell transplantation;
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- Primary resistance: induction with 2 courses of anti-CD20 monoclonal antibody-based immunochemotherapy at the time of first treatment, the best curative effect assessed as stable disease or disease progression.
- ECOG score 0 to 1.
- The presence of a measurable lesion that meets one of the following criteria:
- The long axis of the lymph node lesion exceeds 15 mm in length (the short axis is measurable);
- The long and short axes of the extralymph node lesion exceed 10 mm in length.
- Appropriate organ function, with laboratory results within 7 days prior to lymphatic clearance chemotherapy meeting the following criteria.
- Glutathione aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN)
- Glutamic aminotransferase (ALT) ≤ 3 times ULN.
- Total bilirubin ≤ 1.5 times ULN, unless the subject has documented Gilbert syndrome. Subjects with Gilbert-Meulengracht syndrome with total bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN may be included.
- Serum creatinine ≤ 1.5 times ULN or a creatinine clearance ≥ 60 ml/min.
- Haemoglobin ≥ 60 g/L or haemoglobin maintained at that level following transfusion.
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L.
- A platelet count ≥ 30 x 10^9/L or a platelet count maintained at that level following a platelet transfusion
- Left ventricular ejection fraction (LVEF) ≥ 45%.
- Female subjects with of childbearing potential should have a negative pregnancy test during the screening period. Any male and female subjects of childbearing potential must agree to use an effective contraception method for at least six months from the time that they sign the informed consent form until the end of the cell infusion. Female subjects without childbearing potential (meeting at least 1 of the following criteria) is described below.
- Have undergone a hysterectomy or bilateral oophorectomy
- Medically recognised ovarian failure.
- Medically recognised as post-menopausal (at least 12 consecutive months of menopause without pathological or physiological cause).
Who cannot join
- Other malignancies within 5 years prior to screening, except adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer, post-radical localized prostate cancer, post-radical ductal carcinoma in situ, and post-radical thyroid cancer
- Any unstable systemic disease: including but not limited to active infection (other than local infection), unstable angina, cerebrovascular accident or transient ischaemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association class III or IV cardiac insufficiency, refractory hypertension (refractory hypertension is defined as blood pressure that has not reached standard after >1 month of reasonably tolerable treatment with ≥3 antihypertensive drugs (including diuretics) at adequate doses based on lifestyle improvement or blood pressure that is not effectively controlled with ≥4 antihypertensive drugs), severe cardiac arrhythmias requiring pharmacologic treatment, hepatic arrhythmias, liver diseases, kidney diseases or metabolic disorders.
- Patients with B-cell non-Hodgkin's lymphoma with active central nervous system invasion.
- Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titres not within the normal reference range, positive hepatitis C virus (HCV) antibody and peripheral blood HCV RNA ,positive for human immunodeficiency virus (HIV), or positive for cytomegalovirus (CMV) DNA, or positive syphilis test.
- Active or uncontrolled infections requiring systemic treatment (except simple urinary tract infections or upper respiratory tract infections).
- Subjects who are receiving systemic steroids prior to screening and who are judged by the investigator to require long-term treatment with systemic steroids during the treatment period (except for inhaled or topical use).
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- Previous organ transplantation or preparation for organ transplantation (except for haematopoietic stem cell transplantation)
- Persons with acute/chronic Graft-vs-Host Disease (GvHD)
- Patients have received a haematopoietic stem cell transplant within 2 months prior to screening
- Patients have received CAR-T therapy or other gene-modified cell therapy prior to enrolment
- Active neurological autoimmune or inflammatory diseases (e.g. Guillain-Barre Syndrome (GBS), Amyotrophic lateral sclerosis (ALS)) and clinically significant active cerebrovascular disease (e.g. cerebral oedema, Posterior Reversible Encephalopathy Syndrome (PRES)). Encephalopathy Syndrome (PRES)).
- Patients with a life expectancy of less than 3 months
- Patients have been involved in other clinical studies within 3 months prior to screening.
- Patients, in the judgement of the investigator and/or clinical criteria, are contraindicated to any study procedure or have other medical conditions that may place them at unacceptable risk.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310009
Hui Liu, MD, PhD, 086-13819198629, sylen@zju.edu.cn
Wenbin Qian, MD, PhD
About this study
Official title: Clinical Study of the Efficacy of CD19-CAR-DNT Cells in the Treatment of Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
To evaluate the safety and tolerability of CD19-CAR-DNT cells infusion in subjects with relapsed/refractory B-cell non-Hodgkin's Lymphoma
Read the detailed description
This is an open, single-arm, single-dose, dose-escalation and dose-expansion clinical trial designed to evaluate the maximum tolerated dose of CD19-CAR-DNT cells, the safety, the preliminary efficacy and the pharmacokinetic profile of CD19-CAR-DNT cells in vivo after infusion in clinical studies. 9 patients are planned to be enrolled in the dose-escalation trial (1×10^6 CD19-CAR-DNT cells/kg, 3×10^6 CD19-CAR-DNT cells/kg, 9×10^6 CD19-CAR-DNT cells/kg) and 3 patients in the dose-expansion trial. The primary endpoints are DLT, MTD, and the incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
- Conditions
- B-cell Non-Hodgkin's Lymphoma
- Being tested
- CD19-CAR-DNT cells
- Keywords
- r/r B-NHL ,Cell therapy
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19-CAR-DNT cellsBiological
Lentiviral vector-transducted DNT cells to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide and fludarabine lymphodepleting chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| CD19-CAR-DNT cells | Experimental | 9 patientsare planned to be enrolled in the dose-escalation trial (1×10^6 CD19-CAR-DNT cells/kg, 3×10^6 CD19-CAR-DNT cells/kg, 9×10^6 CD19-CAR-DNT cells/kg) and 3 patients in the dose-expansion trial. Receives: Biological: CD19-CAR-DNT cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
To evaluate the safety, tolerability, and determine the recommended dosage of CD19-CAR-DNT Cell Therapy for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Measured: Up to 28 days
MTD
MTD was the highest dose for DLT in ≤1/6 subjects
Measured: Up to 28 days
Incidence of abnormalities
Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
Measured: Up to 28 days
Secondary outcomes (9)
Pharmacokinetics (PK) indicator (Cmax)
The peak concentration of CD19-CAR-DNT cells amplified in the peripheral blood (Cmax, detected by qPCR).
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the area under the curve (AUC). (AUC, detected by qPCR).
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (Tmax)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the peak plasma time (Tmax). Tmax is defined as the time to reach the highest concentration (Tmax, detected by qPCR).
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (T1/2)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the elimination half-life in hours (T1/2). T1/2 is defined as the time point when the concentration of CD19-CAR-DNT reaches half of maximum in a patient's peripheral blood (T1/2, detected by qPCR).
Measured: Up to 90 days
Overall Response Rate
The proportion of CR or PR patients as assessed by investigators based on Lugano 2014 Response Assessment
Measured: Up to 2 years
Disease Control Rate
The percentage of PR, CR and SD patients in the total patient population
Measured: Up to 2 years
Duration of Response
The time from the start of the first assessment of CR or PR to the first assessment as disease recurrence or progression or death
Measured: Up to 2 years
Progression Free Survival
The length of time that a participant's disease did not progress during or after CD19-CAR-DNT treatment.
Measured: Up to 2 years
Overall Survival
From the date of entry into the clinical study until death from any cause
Measured: Up to 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2022
- Study start15 Jun 2022
- Primary completionJun 2024 (estimated)
- Study completionJun 2025 (estimated)
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 Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Zhejiang Ruijiamei Biotechnologies, Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Wenbin Qian, MD, PhD, Principal investigator, 2nd Affiliated Hospital, School of Medicine, Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05453669
- Sponsor's protocol ID
- IR2022000371
- Status last verified
- Jun 2022
- First submitted
- 28 Jun 2022
- Last updated
- 12 Jul 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Xiao X, Liu H, Qiu X, Chen P, Li X, Wang D, Song G, Cheng Y, Yang L, Qian W. CD19-CAR-DNT cells (RJMty19) in patients with relapsed or refractory large B-cell lymphoma: a phase 1, first-in-human study. EClinicalMedicine. 2024 Feb 29;70:102516. doi: 10.1016/j.eclinm.2024.102516. eCollection 2024 Apr.
PubMed 38444429
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of the Efficacy of CD19-CAR-DNT Cells in the Treatment of Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT05453669
- Acronym / sponsor ID
- IR2022000371
- Conditions
- B-cell Non-Hodgkin's Lymphoma
- Keywords
- r/r B-NHL ,Cell therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Zhejiang Ruijiamei Biotechnologies, Co., Ltd.
- Study start
- 15 Jun 2022 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 12 Jul 2022 (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.
To evaluate the safety and tolerability of CD19-CAR-DNT cells infusion in subjects with relapsed/refractory B-cell non-Hodgkin's Lymphoma
Detailed description
This is an open, single-arm, single-dose, dose-escalation and dose-expansion clinical trial designed to evaluate the maximum tolerated dose of CD19-CAR-DNT cells, the safety, the preliminary efficacy and the pharmacokinetic profile of CD19-CAR-DNT cells in vivo after infusion in clinical studies. 9 patients are planned to be enrolled in the dose-escalation trial (1×10^6 CD19-CAR-DNT cells/kg, 3×10^6 CD19-CAR-DNT cells/kg, 9×10^6 CD19-CAR-DNT cells/kg) and 3 patients in the dose-expansion trial. The primary endpoints are DLT, MTD, and the incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD19-CAR-DNT cells | Experimental | Biological: CD19-CAR-DNT cells9 patientsare planned to be enrolled in the dose-escalation trial (1×10^6 CD19-CAR-DNT cells/kg, 3×10^6 CD19-CAR-DNT cells/kg, 9×10^6 CD19-CAR-DNT cells/kg) and 3 patients in the dose-expansion trial. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Voluntarily sign an ICF and expect to complete the study procedures for follow-up examinations and treatment.
- Aged 18 to 75 years (including cut-offs), regardless of gender
- A diagnosis of B-cell non-Hodgkin's lymphoma confirmed by cytology or pathological histology according to WHO 2016 criteria, including pathologically confirmed diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL) and high-grade B-cell lymphoma (HGBCL).
- Relapsed/refractory B-cell non-Hodgkin's lymphoma, provided one of the following conditions is met:
- ECOG score 0 to 1.
Key exclusion criteria (14 listed)
- Other malignancies within 5 years prior to screening, except adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer, post-radical localized prostate cancer, post-radical ductal carcinoma in situ, and post-radical thyroid cancer
- Any unstable systemic disease: including but not limited to active infection (other than local infection), unstable angina, cerebrovascular accident or transient ischaemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association class III or IV cardiac insufficiency, refractory hypertension (refractory hypertension is defined as blood pressure that has not reached standard after >1 month of reasonably tolerable treatment with ≥3 antihypertensive drugs (including diuretics) at adequate doses based on lifestyle improvement or blood pressure that is not effectively controlled with ≥4 antihypertensive drugs), severe cardiac arrhythmias requiring pharmacologic treatment, hepatic arrhythmias, liver diseases, kidney diseases or metabolic disorders.
- Patients with B-cell non-Hodgkin's lymphoma with active central nervous system invasion.
- Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titres not within the normal reference range, positive hepatitis C virus (HCV) antibody and peripheral blood HCV RNA ,positive for human immunodeficiency virus (HIV), or positive for cytomegalovirus (CMV) DNA, or positive syphilis test.
- Active or uncontrolled infections requiring systemic treatment (except simple urinary tract infections or upper respiratory tract infections).
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 |
|---|---|---|
| CD19-CAR-DNT cellsLentiviral vector-transducted DNT cells to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide and fludarabine lymphodepleting chemotherapy. | Biological | CD19-CAR-DNT cells |
Primary outcome
DLT
Time frame: Up to 28 days
To evaluate the safety, tolerability, and determine the recommended dosage of CD19-CAR-DNT Cell Therapy for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
MTD
Time frame: Up to 28 days
MTD was the highest dose for DLT in ≤1/6 subjects
Incidence of abnormalities
Time frame: Up to 28 days
Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
9 secondary outcomes
Pharmacokinetics (PK) indicator (Cmax)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (Tmax)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (T1/2)
Time frame: Up to 90 days
Overall Response Rate
Time frame: Up to 2 years
Disease Control Rate
Time frame: Up to 2 years
Duration of Response
Time frame: Up to 2 years
Progression Free Survival
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 15 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
- Derived from this study: PubMed 38444429Xiao X, Liu H, Qiu X, Chen P, Li X, Wang D, Song G, Cheng Y, Yang L, Qian W. CD19-CAR-DNT cells (RJMty19) in patients with relapsed or refractory large B-cell lymphoma: a phase 1, first-in-human study. EClinicalMedicine. 2024 Feb 29;70:102516. doi: 10.1016/j.eclinm.2024.102516. eCollection 2024 Apr.
- 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.
Wenbin Qian, MD, PhD principal investigator
2nd Affiliated Hospital, School of Medicine, Zhejiang University
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 CD19-CAR-DNT cells in people with B-cell Non-Hodgkin's Lymphoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine 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 24 inclusion and 14 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 12 Jul 2022. 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 Wenbin Qian, MD, PhD (+8613605801032, qianwb@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT (time frame: Up to 28 days). The study lists 3 primary outcomes in all. 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 NCT05453669, 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 12 Jul 2022; AzTrials last refreshed its copy on 8 Nov 2026.