Trial Title:
ALPP CAR-T Cells for ALPP-Positive Advanced Solid Tumors
NCT ID:
NCT06556108
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Cyclophosphamide
Fludarabine
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
ALPP CAR-T cells
Description:
T cells genetically engineered with a CAR targeting ALPP (ALPP CAR) that display specific
reactivity against ALPP target cells
Arm group label:
Arm 1
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Arm group label:
Arm 1
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Arm group label:
Arm 1
Summary:
Alkaline phosphatase (ALP) is a membrane-bound glycoprotein that catalyzes the hydrolysis
of phosphates at alkaline pH values. As one of the earliest discovered oncofetal
antigens, ALP has emerged as a significant biomarker for various malignant tumors, such
as ovarian cancer, breast cancer, trophoblastic tumors, germ cell tumors, endometrial
cancer, testicular tumors, cervical intraepithelial neoplasia, and gastrointestinal
tumors.
Detailed description:
This is a single-center, open-label, study of CAR-T cells for the treatment of the
recurrent/metastatic solid tumors patients who had failed standard therapy.
Objective:
To evaluate the safety and efficacy of CAR-T cells in the treatment of advanced solid
tumors.
Eligibility:
Adults aging 18-70 with advanced solid tumors
Design:
1. Patients will undergo a comprehensive set of screening tests, including imaging
procedures, evaluation of cardiac and pulmonary function, as well as a range of
laboratory assessments.
2. After meeting the eligibility criteria and enrolling in the trial, patients will
undergo leukapheresis for collection of autologous lymphocytes, which will be sent
to manufacturing facilities.
3. Once cells have been manufactured, patients will then proceed to lymphodepleting
chemotherapy followed by the infusion of ALPP CAR T-cells.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Be able to understand and sign the Informed of Consent Document. Be willing to
follow the procedure and protocol of the clinical trial;
2. Age 18-70 (including boundary value), both male and female;
3. Expected life span is more than 3 months from the date of signing the informed
consent;
4. ECOG score 0-1;
5. Metastatic or recurrent solid tumors confirmed by histopathology;
6. Refractory to standard treatment evaluated by radiological assessment;
7. Be able provide fresh or preserved tissue specimen;
8. At least 1 measurable lesion (according to RECIST 1.1);
9. ALPP expression positivity determined by IHC；
10. The organ marrow function of the subjects meets the following requirements:
1. Marrow function：ANC≥ 1.5×109/L; PLT count≥ 75×109/L; HGB≥ 90 g/L;
2. Coagulation function: Prothrombin Time (PT)≤ 1.5 times the Upper Limit of
Normal (ULN), International Normalized Ratio (INR)≤ 1.5 times ULN, and
Activated Partial Thromboplastin Time (APTT)≤ 1.5 times ULN;
3. Liver function: ALT and AST≤ 2.5 times ULN (in cases of liver
transfer/infiltration, ≤ 5.0 times ULN); Total Bilirubin (TBIL) ≤ 1.5 times ULN
(with Gilbert's syndrome, <3×ULN);
4. Renal function: Serum Creatinine (Cr)≤ 1.5 times ULN or Creatinine Clearance
Rate (CrCl) ≥ 60ml/min;
5. Cardiac function: Left Ventricular Ejection Fractions (LVEF)≥45%;
6. Pulmonary function: Forced Expiratory Volume in the first second (FEV1) ≥ 50%.
11. Prior to the first dose, subjects must have recovered from toxic effects of previous
treatment (CTCAE grade ≤ 1, with the exception of specific criteria such as
"alopecia"), and the investigator determines that the corresponding adverse events
do not pose a safety risk.
12. For male or female subjects of childbearing potential: from the time of signing the
ICF until at least 24 weeks after the last dose, they must agree to practice
abstinence or use effective contraceptive methods, including intrauterine devices,
etc.
Note: Women of childbearing potential who have undergone surgical sterilization
(including hysterectomy, bilateral oophorectomy, or salpingectomy) or who have been
postmenopausal for more than 24 months are considered to have no potential for
pregnancy.
13. A suitable venous access for the necessary blood collection can be established, and
there are no contraindications for leukapheresis.
Exclusion Criteria:
Inclusion criteria:
1. Be able to understand and sign the Informed of Consent Document. Be willing to
follow the procedure and protocol of the clinical trial;
2. Age 18-70 (including boundary value), both male and female;
3. Expected life span is more than 3 months from the date of signing the informed
consent;
4. ECOG score 0-1;
5. Metastatic or recurrent solid tumors confirmed by histopathology;
6. Refractory to standard treatment evaluated by radiological assessment;
7. Be able provide fresh or preserved tissue specimen;
8. At least 1 measurable lesion (according to RECIST 1.1);
9. ALPP expression positivity determined by IHC；
10. The organ marrow function of the subjects meets the following requirements:
1. Marrow function：ANC≥ 1.5×109/L; PLT count≥ 75×109/L; HGB≥ 90 g/L;
2. Coagulation function: Prothrombin Time (PT)≤ 1.5 times the Upper Limit of
Normal (ULN), International Normalized Ratio (INR)≤ 1.5 times ULN, and
Activated Partial Thromboplastin Time (APTT)≤ 1.5 times ULN;
3. Liver function: ALT and AST≤ 2.5 times ULN (in cases of liver
transfer/infiltration, ≤ 5.0 times ULN); Total Bilirubin (TBIL) ≤ 1.5 times ULN
(with Gilbert's syndrome, <3×ULN);
4. Renal function: Serum Creatinine (Cr)≤ 1.5 times ULN or Creatinine Clearance
Rate (CrCl) ≥ 60ml/min;
5. Cardiac function: Left Ventricular Ejection Fractions (LVEF)≥45%;
6. Pulmonary function: Forced Expiratory Volume in the first second (FEV1) ≥ 50%.
11. Prior to the first dose, subjects must have recovered from toxic effects of previous
treatment (CTCAE grade ≤ 1, with the exception of specific criteria such as
"alopecia"), and the investigator determines that the corresponding adverse events
do not pose a safety risk.
12. For male or female subjects of childbearing potential: from the time of signing the
ICF until at least 24 weeks after the last dose, they must agree to practice
abstinence or use effective contraceptive methods, including intrauterine devices,
etc.
Note: Women of childbearing potential who have undergone surgical sterilization
(including hysterectomy, bilateral oophorectomy, or salpingectomy) or who have been
postmenopausal for more than 24 months are considered to have no potential for
pregnancy.
13. A suitable venous access for the necessary blood collection can be established, and
there are no contraindications for leukapheresis.
Exclusion criteria:
1. Subjects with primary central nervous system (CNS) malignancies; subjects with CNS
metastases who have failed local treatment; subjects without symptomatic brain
metastases within 14 days before pretreatment, or with stable clinical symptoms and
no requirement for corticosteroids or other treatment for brain metastases, may be
included;
2. Prior history of malignancy with non-target indications within the past 5 years,
with the exception of: adequately treated malignancies, with more than 5 years of
stability and minimal risk of recurrence as judged by the investigator; and in situ
carcinoma without evidence of recurrence after adequate treatment;
3. Subjects with any active autoimmune disease, history of autoimmune disease, or
requiring systemic corticosteroids (≥10 mg/day prednisone equivalent) or
immunosuppressive therapy, or syndromes (subjects with skin diseases that do not
require systemic treatment or have resolved childhood asthma/allergies without any
intervention as an adult; subjects with stable thyroid hormone replacement therapy
for autoimmune hypothyroidism may be included);
4. History of immunodeficiency, including positive HIV testing or other acquired or
congenital immunodeficiency diseases;
5. History of hereditary or acquired bleeding disorders;
6. Presence of cardiovascular clinical conditions or symptoms, including: a. History of
thromboembolic events ≥ grade 3 in the past 6 months, or currently receiving
thrombolytic or anticoagulant therapy due to high thrombotic risk; b. Chronic heart
failure with reduced ejection fraction (NYHA class ≥ II); c. History of unstable
angina; d. Myocardial infarction in the past 6 months; e. Clinically significant
malignant arrhythmias (excluding atrial fibrillation, paroxysmal supraventricular
tachycardia); f. Clinically significant QTcF prolongation (QTcF > 450 ms for males,
QTcF > 470 ms for females, derived from Fridericia's formula); g. Poorly controlled
hypertension.
7. Presence of active infection (fever due to tumor growth may be included as judged by
the investigator);
8. Active pulmonary tuberculosis detected by history or CT scan, or history of active
pulmonary tuberculosis within the past 1 year before inclusion, or history of active
pulmonary tuberculosis more than 1 year ago without proper treatment;
9. Patients with active hepatitis B or hepatitis C virus infection (active hepatitis B
defined as hepatitis B virus deoxyribonucleic acid (HBV-DNA) > the lower limit of
detection; active hepatitis C defined as hepatitis C virus ribonucleic acid
(HCV-RNA) > the lower limit of detection) or positive syphilis serology;
10. Pregnant or lactating women, or subjects with a positive blood pregnancy test;
11. Serious surgery or major trauma within 28 days before lymphodepletion;
12. Vaccination with live or attenuated vaccines within 28 days before Lymphodepletion;
13. Systemic corticosteroids (excluding inhaled therapy, topical treatment, or
physiological replacement therapy) or other immunosuppressive treatments within 14
days before lymphodepletion;
14. Receiving any investigational drug or participating in another clinical study within
28 days before lymphodepletion (except for subjects participating in observational,
non-interventional clinical studies, or in the survival follow-up period of an
interventional clinical study);
15. Refractory or persistent seizures, significant pleural or abdominal effusions,
active gastrointestinal bleeding, or subjects judged by the investigator to be at
high risk of significant bleeding due to tumor necrosis;
16. Concomitant severe organic or psychiatric diseases;
17. Prior history of allogeneic bone marrow or solid organ transplantation, or renal
replacement therapy;
18. Under the investigator's judgment, subjects with uncontrollable tumor-related pain
or compression symptoms due to a large tumor burden that requires palliative
treatment or radiation therapy should have completed treatment before entering the
study;
19. History of substance abuse, or alcohol or drug abuse;
20. Prior cellular therapy (TCR-T, CAR-T, TIL, etc);
21. Prior severe allergic reaction to any drug or its components in this trial;
22. Subjects whose condition is judged by the investigator to be unsuitable for this
study.
Gender:
All
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Hematology, Xinqiao Hospital
Address:
City:
ChongQing
Zip:
400037
Country:
China
Status:
Recruiting
Contact:
Last name:
Ruihao Huang, MD
Phone:
18984398751
Phone ext:
+86
Email:
1169731117@qq.com
Start date:
January 1, 2018
Completion date:
January 30, 2026
Lead sponsor:
Agency:
Xinqiao Hospital of Chongqing
Agency class:
Other
Source:
Xinqiao Hospital of Chongqing
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06556108
