CD70-positive Advanced Urologic NeoplasmsPhase 1NCT05990621
Anti-CD70 CAR-T Cell Injection in Patients With CD70-positive Advanced Urologic Neoplasms
A Phase 1 study testing Anti-CD70 CAR-T cells in people with CD70-positive Advanced Urologic Neoplasms, run by Changhai Hospital at 1 site in China.
Trial summary
This is a single-arm, open-label, exploratory clinical study to evaluate the safety, tolerability and preliminary efficacy of Anti-CD70 CAR-T cell injection in patients with CD70-positive Advanced Urologic Neoplasms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CD70-positive Advanced Urologic Neoplasms
- What is being tested?
- Anti-CD70 CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 31 Jul 2023to 31 Mar 2026
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Subject is≥18 years old (including cut-off value), gender is not limited. 2. Histopathologically confirmed tumors of the urinary system (including renal cancers and urothelial cancers). Renal cancers should have failed after targeted therapy and/or immunotherapy. Urothelial cancers should have failed after chemotherapy and/or immunotherapy. Or subjects are unable to tolerate or lack effective therapies.
- 3. At least one measurable lesion according to RECIST v1.1. 4. CD70 should be positive confirmed by Immunohistochemistry/Immunocytochemistry/ Flow Cytometry (IHC/ICC/FCM) in tumor tissue samples.
- 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Life expectancy ≥ 3 months. 7. Adequate function defined as: Hematological functions: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (Patients should not receive G-CSF support within 7 days before laboratory examination); Absolute Lymphocyte Count (ALC) ≥ 0.5 × 109/L; Hemoglobin (HGB) ≥ 80 g/L (Patients should not be transfused red cells within 7 days before the laboratory examination); Platelet count (PLT) ≥ 75 × 109/L (Patients should not receive transfusion support within 7 days before the laboratory examination).
- Hepatic functions: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN); AST and ALT of patients with liver metastasis ≤ 5 × ULN; Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with liver metastasis must ≤ 3.0 × ULN; TBIL of patients with Gilbert's Syndrome ≤ 3.0 × ULN and Direct bilirubin (DBIL) ≤ 1.5 × ULN.
- Coagulation functions: International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (Except for patients who are receiving therapeutic anticoagulants.).
- Renal functions: Serum creatinine (Cr) ≤ 1.5 × ULN; or Estimated glomerular filtration rate (eGFR) ≥30ml/(min·1.73 m2)(Calculated by CKD⁃EPI).
- Cardiac functions: Left ventricular ejection fraction (LVEF) > 50%; Pulmonary function: Oxygen saturation (SpO2) > 92%. 8. Female participants of childbearing potential must undergo a pregnancy test and the results must be negative. Female participants of childbearing potential or male participants whose sex partner has childbearing potential must be willing to use effective methods of contraception from screening period to at least 1 year after infusion.
- 9. Participants must be able to understand the protocol and be willing to enroll the study, sign the informed consent, and be able to comply with the study and follow-up procedures.
Who cannot join
- 1. Patients have received systemic therapy with cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives (which is shorter) prior to signing informed consent; Patients have received systemic glucocorticoids (prednisone at a dose of ≥10 mg per day or equivalent) or other immune-suppressive therapy within 2 weeks prior to signing informed consent; Patients have received systemic antitumor therapy with a biologic agent or other approved targeted small-molecule inhibitor within 1 week or five half-lives (which is shorter) prior to signing informed consent; Patients have received Chinese herbal medicine or Chinese patent medicine with anti-tumor indication within 1 week prior to signing informed consent.
- 2. Pregnant or lactating women. 3. Patients with hepatitis B surface antigen (HBsAg) positive. Patients who is hepatitis B core antibody (HBcAb) positive and the quantification of HBV DNA in peripheral blood is higher than the lower limit of detection. Patients who is hepatitis C virus (HCV) antibody positive and quantification of HCV DNA in peripheral blood is higher than the lower limit of detection. Patients with human immunodeficiency virus (HIV) antibody positive. Patients with syphilis antibody positive and tolulized red unheated serum test (TRUST) titer ≥ 1:4.
- 4. The toxicities caused by the prior therapy (surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) have not recovered to grade 1 according to CTCAE, except for hair loss and peripheral sensory nerve disorders.
- 5. Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.) 6. Patients have received anti-CD70 CAR-T cell therapy. 7. Patients who have history of major surgery and unrecovered severe trauma within 4 weeks prior to signing informed consent; or plan to have major surgery within 12 weeks of cell therapy.
- 8. Presence of known central nervous system metastases, but the following patients will be allowed: a) Asymptomatic brain metastases; b) Clinically stable (no radiographic progression within 4 weeks before apheresis and return of any neurologic symptoms to baseline), and with no need for corticosteroids or other treatment for brain metastases for ≥ 4 weeks.
- 9. Patients with clinically significant systemic disease (such as: severe active infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ dysfunction) that evaluated by the investigator would impair the patients' ability to tolerate the treatments used in this study or significantly increase the risk of complications.
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- Uncontrolled severe active infection (sepsis, bacteremia, viremia, etc.);
- Congestive heart failure with New York Heart Association (NYHA) functional class > 1;
- Clinically significant severe aortic stenosis and symptomatic mitral stenosis;
- Electrocardiogram QTc > 450 msec or QTc > 480 msec in patients with bundle-branch block;
- Uncontrolled clinically significant arrhythmia within 6 months prior to signing informed consent;
- Acute coronary syndrome (such as: unstable angina, myocardial infarction) within 6 months prior to signing informed consent;
- Drug-uncontrolled hypertension (systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 100 mmHg) or pulmonary hypertension;
- Cerebrovascular accident occurred within 6 months prior to signing informed consent, including transient ischemic attack (TIA), cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage;
- A history of active, chronic, or recurrent (within 1 year prior to signing informed consent) severe autoimmune disease or immune-mediated disease requiring steroids or other immunosuppressive therapy, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, autoimmune thyroid disease, multiple sclerosis. Exceptions: hypothyroidism that can be controlled only by hormone replacement therapy, skin diseases (such as: vitiligo, psoriasis) that do not require systemic treatment, coeliac disease that has been controlled; 10. Any form of primary or secondary immunodeficiency, such as severe combined immunodeficiency (SCID); 11. History of severe systemic hypersensitivity reaction to the drugs/ingredients [fludarabine, cyclophosphamide, dimethyl sulfoxide (DMSO), low molecular dextran, human serum albumin (HSA), etc.] used in this study.
- 12. Patients have received attenuated vaccine within 4 weeks prior to signing informed consent.
- 13. Patients have received other clinical trials within 4 weeks prior to signing informed consent.
- 14. History of another malignancy tumor within the previous five years, except for adequately treated non-melanoma skin cancer, carcinoma in situ of bladder, stomach, colon, cervix/dysplasia, melanoma, or breast.
- 15. History of neuropsychiatric diseases diagnosed by the ICD-11 criteria or evaluated by investigator, including but not limited to epilepsy, schizophrenia, dementia, drug and alcohol addictions.
- 16. For any other reasons, the patients are believed not suitable for participation in this study by investigators.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Changhai Hospital
Shanghai, Shanghai Municipality
Yewei Bao, 13612400566, 16ywbao@alumni.stu.edu.cn
About this study
Official title: A Single-arm, Open-label, Dose-escalation/Expansion, Early-phase Clinical Study of Anti-CD70 CAR-T Cell Injection in Patients With CD70-positive Advanced Urological Neoplasms
This is a single-arm, open-label, exploratory clinical study to evaluate the safety, tolerability and preliminary efficacy of Anti-CD70 CAR-T cell injection in patients with CD70-positive Advanced Urologic Neoplasms.
Read the detailed description
This study will include two parts, dose escalation phase (accelerated titration and 3+3 design) followed by a dose expansion phase. All eligible participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by CAR-T cell injection.
The dose escalation phase will determine the maximum tolerated dose (MTD) of Anti-CD70 CAR-T cell injection. Additional patients will be enrolled in the dose expansion phase to further characterize the safety profile and evaluate the efficacy of Anti-CD70 CAR-T cell injection, and establish recommended phase 2 dose (RP2D).
- Being tested
- Anti-CD70 CAR-T cells
- Keywords
- Anti-CD70 CAR-T, Urologic Neoplasms
- Medical subject headings
- Urologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD70 CAR-T cellsBiological
0.6×106/Kg ～ 5.0×106/Kg; cells will be infused intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Anti-CD70 CAR-T cells | Experimental | Anti-CD70 CAR-T cells are autologous genetically modified T cells. Receives: Biological: Anti-CD70 CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AEs)
Incidence and severity of adverse events.
Measured: 2 years
Serious Adverse Events (SAEs)
Incidence and severity of serious adverse events.
Measured: 2 years
Adverse Events of Special Interest (AESI)
Incidence and severity of adverse event of special interest.
Measured: 2 years
Identification of Maximum Tolerated Dose (MTD)
Incidence and severity of dose-limiting toxicities (DLTs) following infusion of UCL70802 cell injection, at each dose level tested in dose escalation phase.
Measured: 4 weeks after the CAR-T cells infusion
Secondary outcomes (7)
Objective Response Rate (ORR)
The Objective Response Rate (ORR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.
Measured: 2 years
Duration of Overall Response (DOR)
Time from documentation of disease response to disease progression.
Measured: 2 years
Progression-Free Survival (PFS)
PFS is defined as the time from CAR-T infusion to the date of the disease progression or death from any cause.
Measured: 2 years
Overall Survival (OS)
OS is defined as the time from CAR-T infusion to the date of death due to any cause.
Measured: 2 years
Bio-distribution of Anti-CD70 CAR-T cells
CAR copies will be measured by qPCR to evaluate the expansion and persistence of CAR-T cells in vivo.
Measured: 2 years
Cytokine Level in Peripheral Blood
Level of cytokines (IFN-γ, IL-6, IL-2, etc.) in serum.
Measured: 2 years
Number of participants with anti-drug antibodies.
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 posted14 Aug 2023
- Study start31 Jul 2023
- Primary completion31 Jan 2026 (estimated)
- Study completion31 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CD70-positive Advanced Urologic NeoplasmsStudies of the same condition, open and under way.
- More trials run by Changhai 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Accelerated titration and 3+3 design dose escalation phase followed by dose expansion phase
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changhai Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- UTC Therapeutics Inc.
- Responsible party
- Sponsor
- Investigators
- Linhui Wang, Principal investigator, Changhai Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05990621
- Sponsor's protocol ID
- Anti-CD70 CAR-T Cell Injection
- Status last verified
- Aug 2023
- First submitted
- 7 Aug 2023
- Last updated
- 14 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open-label, Dose-escalation/Expansion, Early-phase Clinical Study of Anti-CD70 CAR-T Cell Injection in Patients With CD70-positive Advanced Urological Neoplasms
- ClinicalTrials.gov ID
- NCT05990621
- Acronym / sponsor ID
- Anti-CD70 CAR-T Cell Injection
- Keywords
- Anti-CD70 CAR-T, Urologic Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Changhai HospitalUniversity, hospital or other
- Collaborators
- UTC Therapeutics Inc.
- Study start
- 31 Jul 2023 (actual)
- Primary completion
- 31 Jan 2026 (estimated)
- Study completion
- 31 Mar 2026 (estimated)
- First posted
- 14 Aug 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.
This is a single-arm, open-label, exploratory clinical study to evaluate the safety, tolerability and preliminary efficacy of Anti-CD70 CAR-T cell injection in patients with CD70-positive Advanced Urologic Neoplasms.
Detailed description
This study will include two parts, dose escalation phase (accelerated titration and 3+3 design) followed by a dose expansion phase. All eligible participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by CAR-T cell injection.
The dose escalation phase will determine the maximum tolerated dose (MTD) of Anti-CD70 CAR-T cell injection. Additional patients will be enrolled in the dose expansion phase to further characterize the safety profile and evaluate the efficacy of Anti-CD70 CAR-T cell injection, and establish recommended phase 2 dose (RP2D).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Accelerated titration and 3+3 design dose escalation phase followed by dose expansion phase
| Arm | Type | Receives |
|---|---|---|
| Anti-CD70 CAR-T cells | Experimental | Biological: Anti-CD70 CAR-T cellsAnti-CD70 CAR-T cells are autologous genetically modified T cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 1. Subject is≥18 years old (including cut-off value), gender is not limited. 2. Histopathologically confirmed tumors of the urinary system (including renal cancers and urothelial cancers). Renal cancers should have failed after targeted therapy and/or immunotherapy. Urothelial cancers should have failed after chemotherapy and/or immunotherapy. Or subjects are unable to tolerate or lack effective therapies.
- 3. At least one measurable lesion according to RECIST v1.1. 4. CD70 should be positive confirmed by Immunohistochemistry/Immunocytochemistry/ Flow Cytometry (IHC/ICC/FCM) in tumor tissue samples.
- 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Life expectancy ≥ 3 months. 7. Adequate function defined as: Hematological functions: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (Patients should not receive G-CSF support within 7 days before laboratory examination); Absolute Lymphocyte Count (ALC) ≥ 0.5 × 109/L; Hemoglobin (HGB) ≥ 80 g/L (Patients should not be transfused red cells within 7 days before the laboratory examination); Platelet count (PLT) ≥ 75 × 109/L (Patients should not receive transfusion support within 7 days before the laboratory examination).
- Hepatic functions: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN); AST and ALT of patients with liver metastasis ≤ 5 × ULN; Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with liver metastasis must ≤ 3.0 × ULN; TBIL of patients with Gilbert's Syndrome ≤ 3.0 × ULN and Direct bilirubin (DBIL) ≤ 1.5 × ULN.
- Coagulation functions: International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (Except for patients who are receiving therapeutic anticoagulants.).
Key exclusion criteria (20 listed)
- 1. Patients have received systemic therapy with cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives (which is shorter) prior to signing informed consent; Patients have received systemic glucocorticoids (prednisone at a dose of ≥10 mg per day or equivalent) or other immune-suppressive therapy within 2 weeks prior to signing informed consent; Patients have received systemic antitumor therapy with a biologic agent or other approved targeted small-molecule inhibitor within 1 week or five half-lives (which is shorter) prior to signing informed consent; Patients have received Chinese herbal medicine or Chinese patent medicine with anti-tumor indication within 1 week prior to signing informed consent.
- 2. Pregnant or lactating women. 3. Patients with hepatitis B surface antigen (HBsAg) positive. Patients who is hepatitis B core antibody (HBcAb) positive and the quantification of HBV DNA in peripheral blood is higher than the lower limit of detection. Patients who is hepatitis C virus (HCV) antibody positive and quantification of HCV DNA in peripheral blood is higher than the lower limit of detection. Patients with human immunodeficiency virus (HIV) antibody positive. Patients with syphilis antibody positive and tolulized red unheated serum test (TRUST) titer ≥ 1:4.
- 4. The toxicities caused by the prior therapy (surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) have not recovered to grade 1 according to CTCAE, except for hair loss and peripheral sensory nerve disorders.
- 5. Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.) 6. Patients have received anti-CD70 CAR-T cell therapy. 7. Patients who have history of major surgery and unrecovered severe trauma within 4 weeks prior to signing informed consent; or plan to have major surgery within 12 weeks of cell therapy.
- 8. Presence of known central nervous system metastases, but the following patients will be allowed: a) Asymptomatic brain metastases; b) Clinically stable (no radiographic progression within 4 weeks before apheresis and return of any neurologic symptoms to baseline), and with no need for corticosteroids or other treatment for brain metastases for ≥ 4 weeks.
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-CD70 CAR-T cells0.6×106/Kg ～ 5.0×106/Kg; cells will be infused intravenously. | Biological | Anti-CD70 CAR-T cells |
Primary outcome
Adverse Events (AEs)
Time frame: 2 years
Incidence and severity of adverse events.
Serious Adverse Events (SAEs)
Time frame: 2 years
Incidence and severity of serious adverse events.
Adverse Events of Special Interest (AESI)
Time frame: 2 years
Incidence and severity of adverse event of special interest.
Identification of Maximum Tolerated Dose (MTD)
Time frame: 4 weeks after the CAR-T cells infusion
Incidence and severity of dose-limiting toxicities (DLTs) following infusion of UCL70802 cell injection, at each dose level tested in dose escalation phase.
7 secondary outcomes
Objective Response Rate (ORR)
Time frame: 2 years
Duration of Overall Response (DOR)
Time frame: 2 years
Progression-Free Survival (PFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Bio-distribution of Anti-CD70 CAR-T cells
Time frame: 2 years
Cytokine Level in Peripheral Blood
Time frame: 2 years
Number of participants with anti-drug antibodies.
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
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.
Linhui Wang principal investigator
Changhai Hospital
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 Anti-CD70 CAR-T cells in people with CD70-positive Advanced Urologic Neoplasms, run by Changhai 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 8 inclusion and 20 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 14 Aug 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 Yewei Bao (13612400566, 16ywbao@alumni.stu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (AEs) (time frame: 2 years). The study lists 4 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 14 Aug 2023.