Relapsed/Refractory T-cell LymphomaPhase 1NCT06696846
CD70-CAR-NK Cell Therapy for T Cell Lymphoma and Acute Myeloid Leukemia
A Phase 1 study testing CD70 CAR-NK in people with Relapsed/Refractory T-cell Lymphoma and Relapsed/Refractory Acute Myeloid Leukemia, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
CD70 is a promising target for immunotherapy because it is overexpressed in T-cell lymphoma (TCL) and acute myeloid leukemia (AML) tumor cells but is found in deficient levels in normal tissues and hematopoietic stem cells. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Relapsed/Refractory T-cell Lymphoma, Relapsed/Refractory Acute Myeloid Leukemia
- What is being tested?
- CD70 CAR-NK
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2024to 30 Nov 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- According to the WHO disease classification, patients with relapsed/refractory T - lymphoma and acute myeloid leukemia:
- Voluntarily participate in this study and sign the informed consent form;
- Aged between 18-75 years old, both male and female are eligible;
- Relapsed/refractory T cell lymphoma is defined as: relapsed/refractory after having received at least two or more lines of previous treatment (patients with anaplastic large -cell lymphoma must have been exposed and resistant to Brentuximab vedotin). The celluar subtypes of T-cell lymphoma include: angioimmunoblastic T-cell lymphoma; peripheral T - cell lymphoma not otherwise specified; ALK-negative anaplastic large - cell lymphoma; Relapsed/refractory AML is defined as: leukemia cells reappear in the peripheral blood after complete remission or the blasts in the bone marrow ≥ 5% or the extramedullary leukemia infiltration outside. Or newly diagnosed cases did not achieve a CR after two courses of standard regimens; those who relapse within 12 months after CR after consolidation and intensification treatment; those who relapse after 12 months and have not responded to conventional chemotherapy; those who relapse two or more times; those with persistent extramedullary leukemia;
- The expected survival period ≥ 12 weeks;
- CD70 expression is positive in tumor tissue puncture sections/tumor cells detected by flow cytometry, and the number of CD70 - positive cells detected by immunohistochemistry ≥ 20% (++ or more);
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- ECOG score is 0 - 2;
- Adequate organ function reserve:
- Alanine aminotransferase and aspartate aminotransferase ≤ 2.5× UNL;
- Creatinine clearance rate (Cockcroft - Gault method) ≥ 60 mL/min;
- Serum total bilirubin and alkaline phosphatase ≤ 1.5× UNL;
- Glomerular filtration rate > 50 ml/min;
- Cardiac ejection fraction ≥ 45%;
- Under indoor natural air environment, the basic oxygen saturation > 92%;
- Routine blood test: absolute neutrophil count > 1000/mm3, platelet count ≥ 45×109, hemoglobin ≥ 8.0g/dl (the standard for AML patients is ≥ 7.0g/dl; blood transfusion is allowed);
- Previous autologous hematopoietic stem cell transplantation is allowed once;
- Patients who have previously received CAR - T cell therapy and were evaluated as ineffective after 3 months or relapsed after CR are allowed;
- Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial period;
- No active lung infection, and indoor air blood oxygen saturation ≥ 92%;
- Before the study drug is used, approved anti - tumor treatment methods, such as systemic chemotherapy, whole - body radiotherapy, and immunotherapy, have been completed for at least 3 weeks; the wash - out period for targeted drug regimens without chemotherapy is 2 weeks;
- Two negative tests for COVID - 19 or influenza A.
Who cannot join
- Subjects meeting any of the following criteria will not be eligible for this study:
- Those with a history of allergy to any component in the cellular product;
- Those with a history of other tumors;
- Those who had grade II - IV (Glucksberg criteria) acute GvHD or extensive chronic GvHD after previous allogeneic hematopoietic stem cell transplantation; or those who are currently receiving anti - GvHD treatment;
- Those who have received gene therapy within the past 3 months;
- Those with active infections requiring treatment (except for simple urinary tract infections and bacterial pharyngitis). However, prophylactic antibiotic, antiviral, and antifungal treatments are permitted;
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- Subjects with hepatitis B (HBsAg - positive, but HBV - DNA < 103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis, and other acquired or congenital immunodeficiency diseases, including but not limited to those infected with the AIDS virus;
- Subjects with grade III or IV cardiac insufficiency according to the New York Heart Association cardiac function classification standard of the United States;
- Those whose toxic reactions from previous anti - tumor treatment have not recovered (CTCAE 5.0 toxic reactions have not recovered to ≤ grade 1, except for fatigue, anorexia, and alopecia);
- Subjects with a history of epilepsy or other central nervous system diseases;
- Lactating women who are unwilling to stop breastfeeding;
- Any other circumstances that, in the opinion of the investigator, may increase the risk to the subject or interfere with the test results;
- Those with positive nucleic acid tests for COVID - 19 or influenza A.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Yang Xu, Ph.D contact
China1 site, 1 recruiting
- Recruiting
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310009
Yang Xu, +86-571-87913679, yxu@zju.edu.cn
About this study
Official title: Cord Blood-derived CD70-targeting CAR-NK Cell Therapy for Refractory/Relapsed T Cell Lymphoma and Acute Myeloid Leukemia
CD70 is a promising target for immunotherapy because it is overexpressed in T-cell lymphoma (TCL) and acute myeloid leukemia (AML) tumor cells but is found in deficient levels in normal tissues and hematopoietic stem cells. This study aims to evaluate the safety and efficacy of CD70-targeted CAR-NK (CD70-CAR-NK) cells in patients with relapsed and refractory TCL and AML.
Read the detailed description
Despite significant advances in CAR-T cell therapy for refractory and relapsed B-cell malignancies and multiple myeloma, CAR-T therapy for T cell lymphoma and acute myeloid leukemia only resulted in suboptimal response partly due to the lack of an ideal target and possible fratricide. Chimeric antigen receptor (CAR)-NK cells may have advantages over CAR-T cells, such as reducing cytokine release and preventing fratricide and tumor contamination in T-cell lymphoma. CD70, which is overexpressed in tumor cells in T cell lymphoma and AML but minimally in normal tissues or hematopoietic stem cells, has emerged as a novel immunotherapy target. Inhibition of the growth of CD70-positive tumors through blocking the CD70/CD27 pathway potentially led to clinical response in relapsed/refractory T-cell lymphoma and AML.
In preclinical studies, we and others have shown that CD70 CAR-NK cells effectively suppress the growth of lymphoma and AML xenograft in vivo, extending the survival of tumor-bearing mice but without significant toxicities. This study aims to evaluate the safety, pharmacokinetics, and efficacy of CD70-targeted CAR-NK cells in patients with CD70-positive relapsed/refractory T-cell lymphoma and AML.
- Being tested
- CD70 CAR-NK
- Keywords
- CD70, CAR-NK, T cell lymphoma, acute myeloid leukemia
- Medical subject headings
- Lymphoma, T-Cell, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD70 CAR-NKBiological
CAR - NK cells constructed by using genetic engineering technology retain the original extensive tumor - killing ability of NK cells. By using their unique target cell recognition mechanism, the target is accurately locked on specific antigen proteins, thereby enhancing the anti - tumor effect. Cord blood-derived CAR - NK cell products shorten the treatment time and are inexpensive. Multiple studies have confirmed the feasibility of CAR - NK cells in treating hematological tumors.
Blocking the CD70/CD27 signaling pathway plays an important role in inhibiting CD70 - positive tumors, such as refractory/relapsed T - cell lymphoma and acute myeloid leukemia. Pre - clinical studies in our laboratory have proved that CD70 CAR - NK can effectively inhibit the in - vivo and in - vitro proliferation of T - cell lymphoma and prolong survival.
| Study group | Role | What they receive |
|---|---|---|
| CD70 CAR-NK for the treatment of CD70-positive relapsed/refractory T-cell lymphoma and AML | Experimental | The first stage is a dose escalation study, with three CD70 CAR-NK dose levels. Each dose level is planned to recruit 3 to 6 subjects to evaluate safety and efficacy and determine the number of CD70 CAR-NK cells for treatment in the second stage. The second stage is the dose expansion stage, where 30 subjects are recruited to receive the number of CD70 CAR-NK cells recommended in the first stage. Receives: Biological: CD70 CAR-NK |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence and type of dose-limiting toxicity (DLT) within 28 days
To determine the incidence and type of dose-limiting toxicity (DLT) within 28 days after CD70-CAR - NK cell infusion
Measured: 28 days
the incidence and severity of treatment-related adverse events as assessed by CTCAE v4.0
CAR-NK treatment-related AEs include CRS, ICANS, cytopenia, and other non-hematological toxicities
Measured: within 90 days after CAR-NK infusion
Secondary outcomes (3)
Objective response rate (ORR) at day 30
To evaluate the overall response rate (PR+CR )as assessed by PET-CT for T cell lymphoma, and by bone marrow examination for AML
Measured: 30 days
duration of response
duration of response measured as the time from the date of first documentation of response to the date of first documented progression
Measured: 2 years
progression-free survival
defined as the time from the date of randomization to the date of first documentation of disease progression based on NCCN criteria as evaluated by an independent review committee (IRC), or death due to any cause, whichever occurs first.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2024
- Study start1 Dec 2024
- Primary completion30 Nov 2027 (estimated)
- Study completion30 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06696846
- Sponsor's protocol ID
- 2024-0992
- Status last verified
- Apr 2026
- First submitted
- 12 Nov 2024
- Last updated
- 30 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cord Blood-derived CD70-targeting CAR-NK Cell Therapy for Refractory/Relapsed T Cell Lymphoma and Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT06696846
- Acronym / sponsor ID
- 2024-0992
- Keywords
- CD70, CAR-NK, T cell lymphoma, acute myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 1 Dec 2024 (actual)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 30 Nov 2028 (estimated)
- First posted
- 20 Nov 2024 (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.
CD70 is a promising target for immunotherapy because it is overexpressed in T-cell lymphoma (TCL) and acute myeloid leukemia (AML) tumor cells but is found in deficient levels in normal tissues and hematopoietic stem cells. This study aims to evaluate the safety and efficacy of CD70-targeted CAR-NK (CD70-CAR-NK) cells in patients with relapsed and refractory TCL and AML.
Detailed description
Despite significant advances in CAR-T cell therapy for refractory and relapsed B-cell malignancies and multiple myeloma, CAR-T therapy for T cell lymphoma and acute myeloid leukemia only resulted in suboptimal response partly due to the lack of an ideal target and possible fratricide. Chimeric antigen receptor (CAR)-NK cells may have advantages over CAR-T cells, such as reducing cytokine release and preventing fratricide and tumor contamination in T-cell lymphoma. CD70, which is overexpressed in tumor cells in T cell lymphoma and AML but minimally in normal tissues or hematopoietic stem cells, has emerged as a novel immunotherapy target. Inhibition of the growth of CD70-positive tumors through blocking the CD70/CD27 pathway potentially led to clinical response in relapsed/refractory T-cell lymphoma and AML.
In preclinical studies, we and others have shown that CD70 CAR-NK cells effectively suppress the growth of lymphoma and AML xenograft in vivo, extending the survival of tumor-bearing mice but without significant toxicities. This study aims to evaluate the safety, pharmacokinetics, and efficacy of CD70-targeted CAR-NK cells in patients with CD70-positive relapsed/refractory T-cell lymphoma and AML.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD70 CAR-NK for the treatment of CD70-positive relapsed/refractory T-cell lymphoma and AML | Experimental | Biological: CD70 CAR-NKThe first stage is a dose escalation study, with three CD70 CAR-NK dose levels. Each dose level is planned to recruit 3 to 6 subjects to evaluate safety and efficacy and determine the number of CD70 CAR-NK cells for treatment in the second stage. The second stage is the dose expansion stage, where 30 subjects are recruited to receive the number of CD70 CAR-NK cells recommended in the first stage. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- According to the WHO disease classification, patients with relapsed/refractory T - lymphoma and acute myeloid leukemia:
- Voluntarily participate in this study and sign the informed consent form;
- Aged between 18-75 years old, both male and female are eligible;
- Relapsed/refractory T cell lymphoma is defined as: relapsed/refractory after having received at least two or more lines of previous treatment (patients with anaplastic large -cell lymphoma must have been exposed and resistant to Brentuximab vedotin). The celluar subtypes of T-cell lymphoma include: angioimmunoblastic T-cell lymphoma; peripheral T - cell lymphoma not otherwise specified; ALK-negative anaplastic large - cell lymphoma; Relapsed/refractory AML is defined as: leukemia cells reappear in the peripheral blood after complete remission or the blasts in the bone marrow ≥ 5% or the extramedullary leukemia infiltration outside. Or newly diagnosed cases did not achieve a CR after two courses of standard regimens; those who relapse within 12 months after CR after consolidation and intensification treatment; those who relapse after 12 months and have not responded to conventional chemotherapy; those who relapse two or more times; those with persistent extramedullary leukemia;
- The expected survival period ≥ 12 weeks;
Key exclusion criteria (13 listed)
- Those with a history of allergy to any component in the cellular product;
- Those with a history of other tumors;
- Those who had grade II - IV (Glucksberg criteria) acute GvHD or extensive chronic GvHD after previous allogeneic hematopoietic stem cell transplantation; or those who are currently receiving anti - GvHD treatment;
- Those who have received gene therapy within the past 3 months;
- Those with active infections requiring treatment (except for simple urinary tract infections and bacterial pharyngitis). However, prophylactic antibiotic, antiviral, and antifungal treatments are permitted;
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 |
|---|---|---|
| CD70 CAR-NKCAR - NK cells constructed by using genetic engineering technology retain the original extensive tumor - killing ability of NK cells. By using their unique target cell recognition mechanism, the target is accurately locked on specific antigen proteins, thereby enhancing the anti - tumor effect. Cord blood-derived CAR - NK cell products shorten the treatment time and are inexpensive. Multiple studies have confirmed the feasibility of CAR - NK cells in treating hematological tumors. Blocking the CD70/CD27 signaling pathway plays an important role in inhibiting CD70 - positive tumors, such as refractory/relapsed T - cell lymphoma and acute myeloid leukemia. Pre - clinical studies in our laboratory have proved that CD70 CAR - NK can effectively inhibit the in - vivo and in - vitro proliferation of T - cell lymphoma and prolong survival. | Biological | CD70 CAR-NK for the treatment of CD70-positive relapsed/refractory T-cell lymphoma and AML |
Primary outcome
The incidence and type of dose-limiting toxicity (DLT) within 28 days
Time frame: 28 days
To determine the incidence and type of dose-limiting toxicity (DLT) within 28 days after CD70-CAR - NK cell infusion
the incidence and severity of treatment-related adverse events as assessed by CTCAE v4.0
Time frame: within 90 days after CAR-NK infusion
CAR-NK treatment-related AEs include CRS, ICANS, cytopenia, and other non-hematological toxicities
3 secondary outcomes
Objective response rate (ORR) at day 30
Time frame: 30 days
duration of response
Time frame: 2 years
progression-free survival
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Individual participant dataSharing planned: Yes
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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.
Yang Xu, Ph.D contact
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 CD70 CAR-NK in people with Relapsed/Refractory T-cell Lymphoma and Relapsed/Refractory Acute Myeloid Leukemia, 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 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: looking for participants now, as of the sponsor's last update on 30 Apr 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.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wenbin Qian (+86 0571 87783759, qianwb@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence and type of dose-limiting toxicity (DLT) within 28 days (time frame: 28 days). The study lists 2 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 30 Apr 2026.