Trial Title:
A Clinical Study to Evaluate Safety, Tolerance, Pharmacokinetics and Efficacy of Sc610 Injection for Treating Advanced Urinary System Tumors
NCT ID:
NCT05633589
Condition:
Malignant Tumor of Urinary System (Disorder)
Conditions: Official terms:
Urologic Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Sc610 cell injection
Description:
Peripheral blood mononuclear cells (PBMCs) obtained via apheresis are used for cell
product preparation. PD-1 positive T cells are isolated from PBMCs, are transduced with
lentivirus loaded with "enhanced receptor" and "amplification factor", and cell quantity
are amplified. The obtained Sc610 is used for one-time intravenous infusion.
Arm group label:
Experimental: Sc610 cell injection
Summary:
This is an phase I/IIa, open-lable, single-arm, single-dose escalation and multiple-dose
extention clinical study of cell therapy designed to observe and evaluate the tolerance,
the pharmacokinetic characteristics, the safety and the efficacy of Sc610 cell injection
in the treatment of advanced tumor of urinary system.
Detailed description:
This study consists of two phases: the first phase will be the dose exploration phase
(Phase I), followed by the dose extension phase (Phase II).
In phase I, 3 subjects are enrolled for 1st treatment group, starting with single dose of
Sc610 cell injection of 5.0x10^8. If there is no dose limiting toxicity (DLT) observed, 3
subjects are enrolled into treatment groups successively in sequential order of: 1) group
2: Single dose of Sc610 1.5x10^9; 2) group 3: Single dose of Sc610 5x10^9; and 3) gorup
4: Single dose of Sc610 1.5x10^10.
Starting from the completion of Sc610 reinfusion for first subject of the 1st dose group,
the subject will be observed for no less than one week. If no serious toxic and adverse
events occurrs, Sc610 reinfusion for the second and third subjects will be performed. If
no DLT occurrs by the 14th days after completion of reinfusion for the 3rd subject, The
study will proceed to the next treatment group. If DLT is observed in 1/3 of enrolled
subjects, another 3 subjects will be enrolled. In any of the dose groups, if ≤1/6
subjects have DLT, subject enrollment for the next treatment group will start. If DLT
occurs in ≥2/6 of subjects, the number of subjects in the previous dose group shall be
reviewed. If there were only 3 subjects, 3 more subjects will be enrolled. If DLT occurs
in ≤1/6 subjects, the dose will be defined as the maximum tolerable dose (MTD), and the
dose escalation phase of the study will be completed. If DLT occurs in ≥2/6 subjects in
the first dose group, a dose reduction exploration will be performed or the study will be
terminated upon decision made by the Safety Committee.
In phase II, If no dose limiting toxicity event occurred upon the completion of treatment
in each of the 4 groups. Researcher will decide to select 2-4 dose groups for dose
extension study and will enroll 5-8 subjects for each group.
Certain subjects have the option to receive multiple rounds of Sc610 treatment: 1)
Subjects with unconfirmed disease progression (non iCPD, i.e. iUPD, iSD, iPR) as assessed
by the response to the cell treatment by medical imaging of last round of treatment can
enter multiple rounds of treatment. Subjects with complete remission (iCR) will be
allowed to receive one consolidation treatment；Subjects whose response to the cell
treatment as assessed by medical imaging are disease progression (iCPD), and the
investigator judge that the subjects would be unable to benefit from the treatment of
this study, and need to receive a new treatment or change the treatment method, will fall
off/withdraw from the trial. 2) Before entering the next round of treatment each time,
the percentage of PD-1+T cells in total T cells need to be assayed first, and peripheral
blood monocytes apheresis can be performed if the detection result is≥18% (PBMCs≥3
x10^9). The procedures of preparation, reinfusion, and follow-ups after reinfusion of
Sc610 cell injection are the identical as before. 3) If toxic reaction related to Sc610
greater than grade 3 cells is observed in previous dose (round) of treatment, the dose of
next round will be reduced; If adverse events above grade 3 still occur after dose
reduction, the investigator will make a comprehensive judgment on whether to terminate
the study of this subject. 4) Multiple round treatment is a treatment cycle every 12
weeks. After treatment, follow up until the disease progresses, or start a new anti-tumor
treatment, or fall off, or withdraw from the trial.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years old, regardless of gender;
2. Expected survival >3 months;
3. The physical condition score of the Eastern American Oncology Collaboration Group
(ECOG) equal to 0 or 1;
4. Patients with pathologically confirmed, locally advanced, or recurrent metastatic
advanced urinary system malignant tumors, failed in standard treatment, disease
development after multi-line treatments, and cannot be surgically removed,
including:
1. Renal cell carcinoma: clear cell carcinoma, papillary renal cell carcinoma,
chromophobe cell carcinoma, etc;
2. Urothelial carcinoma: including renal pelvis, ureter, bladder, or urethra
orginated;
3. Prostate adenocarcinoma.
5. According to iRECIST standard, there exists at least one measurable tumor lesion as
shown by CT or MRI. Measurable tumor lesions are defined as the longest diameter
≥10mm and scanning thickness ≤ 5.0mm. For lymph node lesions, the short diameter ≥
15mm;
6. The proportion of peripheral blood PD-1+T cells in total T cells ≥ 18%; and
voluntarily accept the apheresis of peripheral blood mononuclear cells for the
preparation of Sc610 cell injection;
7. Sufficient bone marrow and organ functions:
1. Hematology: neutrophils is equal to or higher than 1.5×10^9/L, platelets is
equal to or higher than 75×10^9/L, hemoglobin is equal to or higher than 80g/L;
total lymphocytes is equal to or higher than 60% of the lower limit of normal
range;
2. Hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) are both eqal to or lower than 3 times the upper limit of normal range
(ULN) (if intrahepatic bile duct cancer exists, equal to lower than 5 times of
ULN); total bilirubin (TBIL) is equal to or lower than 1.5 times of ULN;
3. Renal function: Creatinine (Cr) is equal to or lower than 1.5 times of ULN;
4. Coagulation function: prothrombin time (PT) is equal to or shorter than 1.5
times of ULN or activated partial prothrombin time (APTT) is equal to or
shorter than1.5 times of ULN;
8. Qualified patients with fertility (male and female) must agree to use reliable
contraceptive methods (hormone or barrier method or abstinence, etc.) with their
partners during the trial and at least 90 days after the last medication; The blood
or urine pregnancy test within 7 days before the first administration of the study
drug in women of childbearing age (From menarche to 1 year starting from menopause
is considered fertile) must be negative;
9. Subjects need to be informed of this study before the trial, and voluntarily sign a
written informed consent form.
Exclusion Criteria:
1. Intracranial metastasis or meningeal metastasis with clinical symptoms, or other
evidence indicating that the intracranial metastasis or meningeal metastasis of the
patient has not been controlled, and the vertebral body metastasis that is known or
suspected to cause spinal cord compression, with which the investigator judge that
the patient is not suitable for study enrollment;
2. Patients who have had or are currently suffering from other malignant tumors within
2 years before signing the contract, excluding cured patients with basal cell skin
cancer, in situ cervical carcinoma, and in situ lung cancer;
3. Patients treated with PD-L1 monoclonal antibody (including but not limited to
atezolizumab and duvalizumab) within 12 weeks before collection;
4. Those who have active infection within one week before single collection and need
systematic anti infection treatment at present ;
5. People with interstitial lung disease ;
6. Patients who have received immunotherapy and have ≥ grade 3 IRAE;
7. Patients with active or ever suffered from autoimmune diseases with the possibility
of recurrence (such as systemic lupus erythematosus, rheumatoid arthritis,
vasculitis, etc.), except patients with clinically stable autoimmune thyroid
diseases and well controlled type I diabetes ;
8. The adverse reaction of previous anti-tumor treatment has not recovered to CTCAE 5.0
grade evaluation ≤ 1 (except for the toxicity that the researcher judges is without
risk for safety);
9. Have received anti-tumor treatment within 2 weeks before apheresis, including but
not limit to systemic chemotherapy, radiotherapy, immunotherapy, etc; Nitrosourea or
mitomycin C is defined within 6 weeks before apheresis;
10. Have received systemic glucocorticoid (prednisone ≥ 10mg/day or equivalent dose of
the same type of drug) or other immunosuppressants within 2 weeks before apheresis;
The following conditions are exempted: intermittent use of glucocorticoids in local,
eye, joint cavity, nose, and inhalation; and short term use of glucocorticoid for
preventive treatment (such as prevention of contrast agent allergy);
11. Have received other unlisted clinical research drugs or treatments within 4 weeks
before apheresis;
12. Hepatitis B: HBsAg (+) or HbeAg (+); Or anti HBe (+)/anti HBc (+), and the hepatitis
B DNA quantitation is higher than the lower detection limit of the research center;
Hepatitis C: Anti HCV positive; Positive Treponema pallidum antibody; Positive HIV
antibody test;
13. Have a history of serious cardiovascular and cerebrovascular diseases, including but
not limit to:
1. Serious cardiac arrhythmia or conduction bockade, such as ventricular
arrhythmia requiring clinical intervention, Ⅱ-Ⅲ degree atrioventricular
blockade, etc;
2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke,
or other cardiovascular and cerebrovascular events ≥Level 3 occurred within 6
months before the first study drug administration;
3. New York Heart Association (NYHA) cardiac function classification ≥ Grade II or
left ventricular ejection fraction (LVEF)≤50%, or with other structural heart
disease that researchers judge as with high risk;
4. Hypertension beyond clinical control.
14. The serous cavity effusion that cannot be controlled clinically is not suitable for
the group according to the judgment of the investigator;
15. Known alcohol or drug dependence;
16. Mental disorders or poor compliance;
17. Pregnant or lactating women;
18. The investigator believes that the subject has a history of other serious systemic
diseases or is not suitable to participate in this clinical study for other
reasons.The adverse reaction of previous anti-tumor treatment has not recovered to
CTCAE 5.0 grade evaluation ≤ 1 (except for the toxicity without safety risk judged
by researchers such as hair loss);
19. Patients with active or had autoimmune diseases that may recur (such as systemic
lupus erythematosus, rheumatoid arthritis, vasculitis, etc.); Except for patients
with clinically stable autoimmune thyroid disease and well controlled type I
diabetes;
20. Have a history of immunodeficiency, including HIV antibody test positive;
21. Hepatitis B (immunological test results do not exclude infectivity) and/or hepatitis
B DNA titer is higher than the lower limit of the detection value of the research
center; And/or hepatitis C (anti HCV antibody positive); And/or treponema pallidum
antibody positive;
22. Have a history of serious cardiovascular and cerebrovascular diseases, including but
not limited to:
1. There are serious cardiac rhythm or conduction abnormalities, such as
ventricular arrhythmia requiring clinical intervention, ⅱ - ⅲ degree
atrioventricular blockade, etc;
2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or
other cardiovascular and cerebrovascular events ≥ grade 3 occurred within 6
months before the cell reinfusion;
3. New York Heart Association (NYHA) cardiac function rating ≥ class II or left
ventricular ejection fraction (LVEF) <50%, or other structural heart disease
with high risk as judged by the investigator;
4. Clinically uncontrollable hypertension;
23. Serous cavity effusion beyond clinical control is not suitable for the enrollment
according to the judgment of the investigator;
24. Known alcohol or drug dependence;
25. Mental disorders or poor compliance;
26. Pregnant or lactating women;
27. The investigator believes that the subject has a history of other serious systemic
diseases or is not suitable to participate in this clinical study due to other
reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
December 15, 2022
Completion date:
October 30, 2024
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05633589
