B-cell Non Hodgkin LymphomaPhase 1NCT05667155
Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma
A Phase 1 study testing CB dualCAR-NK19/70 in people with B-cell Non Hodgkin Lymphoma, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
To study the safety and efficacy of cord blood-derived CAR-NK cells targeting CD19/CD70 in patients with 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 Lymphoma
- What is being tested?
- CB dualCAR-NK19/70
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteChina
- Study dates
- 15 Dec 2022to 30 Dec 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 participate in the study and sign the informed consent;
- Age 18-75, male and female;
- Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other inert B-cell NHL transforming types:
- (1)refractory or recurrent DLBCL and tFL must be approved by 2 line immune disease relapse after chemotherapy treatment; (2) refractory definition large B cell lymphoma (research SCHOLAR - 1 standard) : more than 4 courses first-line immune chemotherapy disease progression; The stable time of the disease is equal to or less than 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; (3) refractory or recurrent MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; (4)always treatment must include CD20 single resistance (unless the subjects for CD20 negative) and anthracycline-based;
- 4. There was at least one measurable lesion with the longest diameter ≥1.5 cm;
- 5. Predicted survival ≥12 weeks;
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- 6. The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive;
- 7. ECOG score 0-2;
- 8. Adequate reserve of organ functions:
- cereal third transaminase, aspartate aminotransferase 2.5 x or less UNL (upper limit of normal);
- creatinine clearance (Cockcroft - Gault method) or 60 mL/min.
- serum total bilirubin and alkaline phosphatase (1.5 x or less UNL.
- glomerular filtration rate > 50 mL/min
- heart ejection fraction (EF) 45% or higher;
- indoor natural air environment, basic oxygen saturation > 92%
- blood routine: neutrophils absolute number > 1000 cells/mm3, platelet count 45 x109, 8.0 g/dL hemoglobin;
- 9. Allowed to have received a previous stem cell transplant
- 10. Approved anti-B-cell lymphoma therapies, such as systemic chemotherapy, systemic radiotherapy and immunotherapy, had been completed for at least 3 weeks before the study. The eluting period of targeted drug regimens without chemotherapy was 2 weeks;
- 11. Patients who had previously received CAR T cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted;
- 12. Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial
- 13. Two tests have come back negative for COVID-19.
Who cannot join
- Allergic to any of the components of cell products;
- History of other tumors;
- Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous allogeneic hematopoietic stem cell transplantation; Or being treated with anti-GVHD;
- Had received gene therapy in the past 3 months;
- Active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed;
- Subjects infected with hepatitis B (HBsAg positive, but HBV-DNA<103 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV-infected persons;
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- Subjects with Grade III or IV cardiac insufficiency according to the New York Heart Association Cardiac Function Grading criteria;
- Patients who received antitumor therapy in the early stage but the toxicity reaction did not recover (CTCAE 5.0 toxicity reaction did not recover to ≤ level 1, except fatigue, anorexia and alopecia);
- Subjects with a history of epilepsy or other central nervous system diseases;
- Skull enhanced CT or MRI showing evidence of central nervous system lymphoma;
- Lactating women who refuse to stop breastfeeding;
- Any other circumstances that the investigator believes may increase the subject's risk or interfere with the test results.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Hanzhou, Zhejiang, 310009
Wenbin Qian, PhD, +8613605801032, qianwb@zju.edu.cn
Hui Liu, PhD, 13819198629, sylen@zju.edu.cn
About this study
To study the safety and efficacy of cord blood-derived CAR-NK cells targeting CD19/CD70 in patients with B-cell non-Hodgkin's lymphoma
Read the detailed description
This is a single-center, open, one-arm, dose-escalation study to observe the safety and efficacy of cord blood-derived dualCAR-NK19/70 cells in patients with B-cell non-Hodgkin lymphoma.9-18 patients are planned to be enrolled in the dose-escalation trial (2×10^6 cells/kg, 4×10^6 cells/kg, 8×10^6 cells/kg) . Each dose was given once a week for 3 weeks.The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled to estimate the safety and efficacy of CB CAR-NK019 under the best dose.
- Conditions
- B-cell Non Hodgkin Lymphoma
- Being tested
- CB dualCAR-NK19/70
- 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.
CB dualCAR-NK19/70Biological
Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19/CD70 CAR and IL15
| Study group | Role | What they receive |
|---|---|---|
| CB dualCAR-NK19/70 | Experimental | All subjects were intravenously administrated with CB dualCAR-NK19/70 Receives: Biological: CB dualCAR-NK19/70 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicity (DLTs)
To evaluate the safety, tolerability, and determine the recommended dosage of cord blood-derived Anti-CD19 CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma
Measured: Up to 28 days
Secondary outcomes (6)
Overall survival (OS)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Measured: Up to 2 years
Overall response rate (ORR)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Measured: Up to 2 years
Duration of response (DOR)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Measured: Up to 2 years
Complete response rate (CR)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Measured: Up to 2 years
Partial response rate (PR)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Measured: Up to 2 years
Progression free survival (PFS)
To determine the anti-tumor effectivity of CB dualCAR-NK19/70
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2022
- Study start15 Dec 2022
- Primary completion1 Jan 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Non Hodgkin 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
- 48 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wenbin Wenbin, Principal investigator, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05667155
- Sponsor's protocol ID
- 2022-088
- Status last verified
- Feb 2023
- First submitted
- 29 Nov 2022
- Last updated
- 6 Feb 2023
- Results posted
- No
- 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 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT05667155
- Acronym / sponsor ID
- 2022-088
- Conditions
- B-cell Non Hodgkin Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 15 Dec 2022 (actual)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 28 Dec 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 study the safety and efficacy of cord blood-derived CAR-NK cells targeting CD19/CD70 in patients with B-cell non-Hodgkin's lymphoma
Detailed description
This is a single-center, open, one-arm, dose-escalation study to observe the safety and efficacy of cord blood-derived dualCAR-NK19/70 cells in patients with B-cell non-Hodgkin lymphoma.9-18 patients are planned to be enrolled in the dose-escalation trial (2×10^6 cells/kg, 4×10^6 cells/kg, 8×10^6 cells/kg) . Each dose was given once a week for 3 weeks.The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled to estimate the safety and efficacy of CB CAR-NK019 under the best dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CB dualCAR-NK19/70 | Experimental | Biological: CB dualCAR-NK19/70All subjects were intravenously administrated with CB dualCAR-NK19/70 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Voluntarily participate in the study and sign the informed consent;
- Age 18-75, male and female;
- Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other inert B-cell NHL transforming types:
- (1)refractory or recurrent DLBCL and tFL must be approved by 2 line immune disease relapse after chemotherapy treatment; (2) refractory definition large B cell lymphoma (research SCHOLAR - 1 standard) : more than 4 courses first-line immune chemotherapy disease progression; The stable time of the disease is equal to or less than 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; (3) refractory or recurrent MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; (4)always treatment must include CD20 single resistance (unless the subjects for CD20 negative) and anthracycline-based;
- 4. There was at least one measurable lesion with the longest diameter ≥1.5 cm;
Key exclusion criteria (12 listed)
- Allergic to any of the components of cell products;
- History of other tumors;
- Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous allogeneic hematopoietic stem cell transplantation; Or being treated with anti-GVHD;
- Had received gene therapy in the past 3 months;
- Active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed;
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 |
|---|---|---|
| CB dualCAR-NK19/70Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19/CD70 CAR and IL15 | Biological | CB dualCAR-NK19/70 |
Primary outcome
Incidence of dose limiting toxicity (DLTs)
Time frame: Up to 28 days
To evaluate the safety, tolerability, and determine the recommended dosage of cord blood-derived Anti-CD19 CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma
6 secondary outcomes
Overall survival (OS)
Time frame: Up to 2 years
Overall response rate (ORR)
Time frame: Up to 2 years
Duration of response (DOR)
Time frame: Up to 2 years
Complete response rate (CR)
Time frame: Up to 2 years
Partial response rate (PR)
Time frame: Up to 2 years
Progression free survival (PFS)
Time frame: Up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- 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 Wenbin principal investigator
2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
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 CB dualCAR-NK19/70 in people with B-cell Non Hodgkin 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 21 inclusion and 12 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 6 Feb 2023. 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, 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?
Incidence of dose limiting toxicity (DLTs) (time frame: Up to 28 days). 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 6 Feb 2023.