Trial Title:
Anti-CD70 CAR-T Cell Injection in Patients With CD70-positive Advanced Urologic Neoplasms
NCT ID:
NCT05990621
Condition:
CD70-positive Advanced Urologic Neoplasms
Conditions: Official terms:
Neoplasms
Urologic Neoplasms
Conditions: Keywords:
Anti-CD70 CAR-T
Urologic Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Accelerated titration and 3+3 design dose escalation phase followed by dose expansion
phase
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Anti-CD70 CAR-T cells
Description:
0.6×106/Kg ～ 5.0×106/Kg; cells will be infused intravenously.
Arm group label:
Anti-CD70 CAR-T cells
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.
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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.
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Changhai Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Yewei Bao
Phone:
13612400566
Email:
16ywbao@alumni.stu.edu.cn
Start date:
July 31, 2023
Completion date:
March 31, 2026
Lead sponsor:
Agency:
Changhai Hospital
Agency class:
Other
Collaborator:
Agency:
UTC Therapeutics Inc.
Agency class:
Industry
Source:
Changhai Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05990621
