Extranodal NK T Cell LymphomaPhase 2NCT05941156
Clinical Study of Anti-CD56-CAR-T in the Treatment of Relapsed/Refractory NK/T Cell Lymphoma /NK Cell Leukemia
A Phase 2 study testing Anti-CD56 CAR T in people with Extranodal NK T Cell Lymphoma and NK-Cell Leukemia, run by The Affiliated Hospital of Xuzhou Medical University at 1 site in China.
Trial summary
To evaluate the safety and efficacy of anti-CD56-CAR T in the treatment of relapsed refractory NK/T cell lymphoma /NK cell leukemia Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Extranodal NK T Cell Lymphoma, NK-Cell Leukemia
- What is being tested?
- Anti-CD56 CAR T
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2023to May 2026
- Phase
- Phase 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 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;
- Male or female patients aged 18-70 years (including 18 and 70 years);
- The patient was diagnosed as NK/T cell lymphoma /NK cell leukemia by pathology or flow cytometry, and currently has no effective treatment options, such as relapse after chemotherapy or hematopoietic stem cell transplantation; Alternatively, patients voluntarily choose to administer anti-CD56-CAR T cells as salvage therapy.
- The following two categories are included:(1)NK/T cell lymphoma;(2) NK cell leukemia.
- Subject:
- (1)There was no remission or residual lesions after treatment, and HSCT (auto/allo-HSCT) was not suitable; (2)Relapse occurred after CR, and HSCT (auto/allo-HSCT) was not suitable; (3)Patients with high risk factors; (4)Relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy.
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- 6. Measurable or evaluable lesions;
- 7. The patient's main tissues and organs function well:
- Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L;
- Renal function: creatinine < 220 μmol/L;
- Lung function: indoor oxygen saturation ≥95%;
- Cardiac function: left ventricular ejection fraction (LVEF) ≥40%.
- 8. The patients had not received any anti-cancer treatment such as chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) within the first 4 weeks of enrollment, and their previous treatment-related toxic reactions had recovered to ≤ grade 1 at the time of enrollment (except low toxicity such as hair loss);
- 9. The patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous infusion;
- 10. Patients with ECOG score ≤2 and expected survival time ≥3 months.
Who cannot join
- Women who are pregnant (urine/blood pregnancy test positive) or breastfeeding;
- Men or women who have planned to become pregnant within the last 1 year;
- The patients were not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment;
- Patients had uncontrollable infectious diseases within 4 weeks prior to enrollment;
- Active hepatitis B/C virus;
- HIV-infected patients;
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- Suffering from a serious autoimmune disease or immunodeficiency disease;
- The patient is allergic to antibodies, cytokines and other macromolecular biological drugs;
- The patient had participated in other clinical trials within 6 weeks prior to enrollment;
- Systemic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);
- Suffers from mental illness;
- The patient has substance abuse/addiction;
- According to the researchers' judgment, the patient had other conditions that were not suitable for inclusion.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221002
Wei Sang, M.D., Ph.D, 13645207648, xyfylbl515@xzhmu.edu.cn
About this study
Official title: Single-center, Open, One-arm Clinical Study of the Safety and Efficacy of Anti-CD56-CAR T Therapy in Relapsed Refractory NK/T Cell Lymphoma /NK Cell Leukemia
To evaluate the safety and efficacy of anti-CD56-CAR T in the treatment of relapsed refractory NK/T cell lymphoma /NK cell leukemia
Read the detailed description
Extranodal NK/TCL is an aggressive disease with a poor prognosis and a 5-year survival rate of less than 50%. In the absence of effective treatment, median survival for advanced disease is only 6-12 months. A retrospective review of the International Peripheral T-Cell Lymphoma Project recently reported that the median overall survival of NK/TCL was 7.8 months, corresponding to the worst survival of all T-cell lymphoma entities. Therefore, despite good results in the combination of chemoracal-chemotherapy strategies, autologous bone marrow transplantation, and L-asparagase in the treatment of recurrent cases, NK/TCL remains difficult to cure, and the need for alternative therapeutic strategies has prompted researchers to explore new molecular targets.
Nerve cell adhesion molecule 1 (NCAM-1) -CD56 is a member of the immunoglobulin superfamily and is a biomarker of nerve cell adhesion molecule and NK cell. CD56 is highly expressed in NK/T cell lymphomas, skeletal muscle tumors, and malignancies with neurological or neuroendocrine differentiation. CD56-CAR T cells can kill CD56+ neuroblastoma, glioma, and SCLC tumor cells in vitro coculture, and CD56R-CAR+T cells can inhibit tumor growth in vivo when tested against CD56+ human neuroblastoma xenogeneic and SCLC models. CD56-CAR T cells have also been reported as a safe and effective treatment for refractory/relapsing rhabdomyosarcoma. This indicates that CD56 CAR has a wide clinical application prospect and strong potential therapeutic value as a new CAR T target.
CD56 CAR T cells constructed by our laboratory can produce more precise killing effect on tumor cells by converting the immune checkpoint PD-1 signal. The results showed that CD56 CAR T cells could be prepared effectively and kill NK/ T-cell lymphoma cell line SNK-6 in vitro. Compared with traditional second-generation CAR T cells, CD56-CAR T cells prepared in our laboratory showed better killing effect on SNK-6 cells in vitro. At present, no clinical studies on CD56 CAR T therapy for NK/T cell lymphoma have been reported. Therefore, in this study, CD56 CAR T was used to treat relapsed and refractory NK/T cell lymphoma /NK cell leukemia to observe its safety and efficacy.
- Conditions
- Extranodal NK T Cell Lymphoma, NK-Cell Leukemia
- Being tested
- Anti-CD56 CAR T
- Keywords
- Anti-CD56 CAR-T
- Medical subject headings
- Lymphoma, Extranodal NK-T-Cell, Leukemia, Large Granular Lymphocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD56 CAR TBiological
CAR T cells were pretreated at -5 days before retransfusion (FC regimen: fludarabine: 30mg/m2×3 days, cyclophosphamide: 750mg/m2×1 day). Anti CD56-CAR T cells were transfused back to the patient 2 days after the end of chemotherapy. 30 to 60 minutes before CAR T cell infusion, patients were given 325 to 650 mg of acetaminophen orally to prevent infusion-related reactions; If fever occurred on the day of CAR T cell infusion, lasted less than 24 hours, and had no other toxicity, it was attributed to the infusion T cell response.
| Study group | Role | What they receive |
|---|---|---|
| CAR-T Cell Infusion | Experimental | Pretreatment was initiated at -5 days prior to CAR T cell reinfusion, and CAR T cell therapy was performed 2 days after completion of chemotherapy. All patients were pretreated with FC regimen, fludarabine: 30mg/m2×3 days, cyclophosphamide: 750mg/m2×1 day. Anti CD56-CAR T cells were transfused back 2 days after chemotherapy. The freeze-thawed cell product solution is injected back into the body as soon as the patient can accept it. The patient's vital signs should be closely monitored throughout the infusion, and oxygen saturation should be measured at 15-minute intervals before, at the end of, and after infusion, and continue until the patient is stable. 30 to 60 minutes before CAR T cell infusion, patients were given 325 to 650 mg of acetaminophen orally to prevent infusion-related reactions; If fever occurred on the day of CAR T cell infusion, lasted less than 24 hours, and had no other toxicity, it was attributed to the infusion T cell response. Receives: Biological: Anti-CD56 CAR T |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
CR+PR.1.Leukemia:Complete Response (CR):Bone marrow blast cells <5%; primitive cells without Auer bodies; without extramedullary leukemia;Absolute blood neutrophil count was> 1.0*10^9 / L (1000 / μ L);Platelet count> 100*10^9 / L (100 000 / μ L);Not dependent on RBC infusion.Partial Response (PR):Only for Phase I and II clinical trials;Bone marrow cells were reduced to 5 - 25% and at least 50% compared with before treatment;Hematological parameters met the same criteria for CR. 2.Lymphoma:CR:All the evidence of the lesions disappeared.PR:The lymph nodes shrank with no new lesions.
Measured: From 1 month to 1 year.
progression-free survival (PFS)
The time between treatment and observation of disease progression or death from any cause.
Measured: From 1 month to 1 year.
overall survival (OS)
The time from the start of treatment to death from any cause.
Measured: From 1 month to 1 year.
event-free survival (EFS)
The time between the start of treatment and the occurrence of any event, including disease recurrence, death, and so on.
Measured: From 1 month to 1 year.
Safety evaluation index
- Detection of CRS-related factors: such as IFN, IL-6, TNF, IL-10, IL-4, CRP, etc;2. Testing of various laboratory items: blood routine, coagulation function, blood film observation, liver function, renal work, electrolytes, blood glucose, cardiac enzymes, blood cells, T cell subsets, immunoglobulins, etc;3.Adverse events and serious adverse events were observed.
Measured: From 1 month to 1 year.
Secondary outcomes (1)
CAR T cell index of correlation
The presence of peripheral blood and bone marrow CAR-T cells were measured regularly by using flow cytometry, quantitative PCR techniques.
Measured: From 1 month to 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2023
- Study start1 May 2023
- Primary completionMay 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extranodal NK T 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Affiliated Hospital of Xuzhou Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05941156
- Sponsor's protocol ID
- XYFY2023-KL123-01
- Status last verified
- Jul 2023
- First submitted
- 17 May 2023
- Last updated
- 12 Jul 2023
- Results posted
- No
- Data monitoring committee
- 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 12 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-center, Open, One-arm Clinical Study of the Safety and Efficacy of Anti-CD56-CAR T Therapy in Relapsed Refractory NK/T Cell Lymphoma /NK Cell Leukemia
- ClinicalTrials.gov ID
- NCT05941156
- Acronym / sponsor ID
- XYFY2023-KL123-01
- Conditions
- Extranodal NK T Cell Lymphoma, NK-Cell Leukemia
- Keywords
- Anti-CD56 CAR-T
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- The Affiliated Hospital of Xuzhou Medical UniversityUniversity, hospital or other
- Study start
- 1 May 2023 (actual)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 12 Jul 2023 (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 efficacy of anti-CD56-CAR T in the treatment of relapsed refractory NK/T cell lymphoma /NK cell leukemia
Detailed description
Extranodal NK/TCL is an aggressive disease with a poor prognosis and a 5-year survival rate of less than 50%. In the absence of effective treatment, median survival for advanced disease is only 6-12 months. A retrospective review of the International Peripheral T-Cell Lymphoma Project recently reported that the median overall survival of NK/TCL was 7.8 months, corresponding to the worst survival of all T-cell lymphoma entities. Therefore, despite good results in the combination of chemoracal-chemotherapy strategies, autologous bone marrow transplantation, and L-asparagase in the treatment of recurrent cases, NK/TCL remains difficult to cure, and the need for alternative therapeutic strategies has prompted researchers to explore new molecular targets.
Nerve cell adhesion molecule 1 (NCAM-1) -CD56 is a member of the immunoglobulin superfamily and is a biomarker of nerve cell adhesion molecule and NK cell. CD56 is highly expressed in NK/T cell lymphomas, skeletal muscle tumors, and malignancies with neurological or neuroendocrine differentiation. CD56-CAR T cells can kill CD56+ neuroblastoma, glioma, and SCLC tumor cells in vitro coculture, and CD56R-CAR+T cells can inhibit tumor growth in vivo when tested against CD56+ human neuroblastoma xenogeneic and SCLC models. CD56-CAR T cells have also been reported as a safe and effective treatment for refractory/relapsing rhabdomyosarcoma. This indicates that CD56 CAR has a wide clinical application prospect and strong potential therapeutic value as a new CAR T target.
CD56 CAR T cells constructed by our laboratory can produce more precise killing effect on tumor cells by converting the immune checkpoint PD-1 signal. The results showed that CD56 CAR T cells could be prepared effectively and kill NK/ T-cell lymphoma cell line SNK-6 in vitro. Compared with traditional second-generation CAR T cells, CD56-CAR T cells prepared in our laboratory showed better killing effect on SNK-6 cells in vitro. At present, no clinical studies on CD56 CAR T therapy for NK/T cell lymphoma have been reported. Therefore, in this study, CD56 CAR T was used to treat relapsed and refractory NK/T cell lymphoma /NK cell leukemia to observe its safety and efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-T Cell Infusion | Experimental | Biological: Anti-CD56 CAR TPretreatment was initiated at -5 days prior to CAR T cell reinfusion, and CAR T cell therapy was performed 2 days after completion of chemotherapy. All patients were pretreated with FC regimen, fludarabine: 30mg/m2×3 days, cyclophosphamide: 750mg/m2×1 day. Anti CD56-CAR T cells were transfused back 2 days after chemotherapy. The freeze-thawed cell product solution is injected back into the body as soon as the patient can accept it. The patient's vital signs should be closely monitored throughout the infusion, and oxygen saturation should be measured at 15-minute intervals before, at the end of, and after infusion, and continue until the patient is stable. 30 to 60 minutes before CAR T cell infusion, patients were given 325 to 650 mg of acetaminophen orally to prevent infusion-related reactions; If fever occurred on the day of CAR T cell infusion, lasted less than 24 hours, and had no other toxicity, it was attributed to the infusion T cell response. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients or their legal guardians voluntarily participate and sign the informed consent;
- Male or female patients aged 18-70 years (including 18 and 70 years);
- The patient was diagnosed as NK/T cell lymphoma /NK cell leukemia by pathology or flow cytometry, and currently has no effective treatment options, such as relapse after chemotherapy or hematopoietic stem cell transplantation; Alternatively, patients voluntarily choose to administer anti-CD56-CAR T cells as salvage therapy.
- The following two categories are included:(1)NK/T cell lymphoma;(2) NK cell leukemia.
- Subject:
Key exclusion criteria (13 listed)
- Women who are pregnant (urine/blood pregnancy test positive) or breastfeeding;
- Men or women who have planned to become pregnant within the last 1 year;
- The patients were not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment;
- Patients had uncontrollable infectious diseases within 4 weeks prior to enrollment;
- Active hepatitis B/C virus;
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-CD56 CAR TCAR T cells were pretreated at -5 days before retransfusion (FC regimen: fludarabine: 30mg/m2×3 days, cyclophosphamide: 750mg/m2×1 day). Anti CD56-CAR T cells were transfused back to the patient 2 days after the end of chemotherapy. 30 to 60 minutes before CAR T cell infusion, patients were given 325 to 650 mg of acetaminophen orally to prevent infusion-related reactions; If fever occurred on the day of CAR T cell infusion, lasted less than 24 hours, and had no other toxicity, it was attributed to the infusion T cell response. | Biological | CAR-T Cell Infusion |
Primary outcome
Overall response rate (ORR)
Time frame: From 1 month to 1 year.
CR+PR.1.Leukemia:Complete Response (CR):Bone marrow blast cells <5%; primitive cells without Auer bodies; without extramedullary leukemia;Absolute blood neutrophil count was> 1.0*10^9 / L (1000 / μ L);Platelet count> 100*10^9 / L (100 000 / μ L);Not dependent on RBC infusion.Partial Response (PR):Only for Phase I and II clinical trials;Bone marrow cells were reduced to 5 - 25% and at least 50% compared with before treatment;Hematological parameters met the same criteria for CR. 2.Lymphoma:CR:All the evidence of the lesions disappeared.PR:The lymph nodes shrank with no new lesions.
progression-free survival (PFS)
Time frame: From 1 month to 1 year.
The time between treatment and observation of disease progression or death from any cause.
overall survival (OS)
Time frame: From 1 month to 1 year.
The time from the start of treatment to death from any cause.
event-free survival (EFS)
Time frame: From 1 month to 1 year.
The time between the start of treatment and the occurrence of any event, including disease recurrence, death, and so on.
Safety evaluation index
Time frame: From 1 month to 1 year.
1. Detection of CRS-related factors: such as IFN, IL-6, TNF, IL-10, IL-4, CRP, etc;2. Testing of various laboratory items: blood routine, coagulation function, blood film observation, liver function, renal work, electrolytes, blood glucose, cardiac enzymes, blood cells, T cell subsets, immunoglobulins, etc;3.Adverse events and serious adverse events were observed.
1 secondary outcome
CAR T cell index of correlation
Time frame: From 1 month to 1 year.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anti-CD56 CAR T in people with Extranodal NK T Cell Lymphoma and NK-Cell Leukemia, run by The Affiliated Hospital of Xuzhou 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 15 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 12 Jul 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: From 1 month to 1 year.). The study lists 5 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 12 Jul 2023.