Advanced Solid Tumors
Conditions
Brief 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.
Interventions
BIOLOGICALALPP CAR-T cells
T cells genetically engineered with a CAR targeting ALPP (ALPP CAR) that display specific reactivity against ALPP target cells
DRUGFludarabine
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
DRUGCyclophosphamide
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Sponsors
Xinqiao Hospital of Chongqing
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity or Maximum Tolerated Dose (MTD) | Day 28 post-initial ALPP CAR-T infusion | Dose Limiting Toxicity (DLT) is defined as patients with the adverse event (AE) or laboratory abnormality assessed by the principal investigator (PI). These should be possibly related to ALPP CAR-T cell therapy, and should be unrelated to the disease itself, disease progression, concomitant diseases or concomitant medication. The MTD is the highest dose at which no more than one out of six patients experiences DLT, or the highest dose level tested if no DLTs are observed across all dose levels. |
| Overall response rate | Day 0 - Day 730 | The efficacy of ALPP CAR-T is assessed by the objective response rate (ORR) according to RECIST 1.1 and iRECIST. ORR is defined as patients who have achieved either a partial response (PR) or a complete response (CR). |
| Treatment-related adverse events as assessed by CTCAE v5.0 | Day 0 - Day 730 | The type, incidence and severity of adverse events include clinically significant post-treatment abnormal laboratory examination results, abnormal physical examination and blood examination results, bone marrow examination results, etc. Clinical and laboratory AEs will be classified according to the National Cancer Institute general terminology standard for adverse events (NCI CTCAE) version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | Day 0 - Day 730 | The efficacy of ALPP CAR-T will be assessed by duration of response (DOR). The DOR refers to the length of time from the first appearance of a treatment response to the first occurrence of progressive disease or recurrence. |
| Progression free survival | Day 0 - Day 730 | The efficacy of ALPP CAR-T will be assessed by progression free survival (PFS). The PFS refers to the time from treatment to progressive disease or death for any reason. |
| Overall survival | Day 0 - Day 730 | The efficacy of ALPP CAR-T will be assessed by overall survival (OS). The OS refers to the time from treatment to death. |
| Expansion and persistence of ALPP CAR-T cells in peripheral blood or serous effusion (if present) | Day 0 - Day 730 | Blood and serous effusion (if present) samples were collected to measure persistence of infused ALPP CAR-T using polymerase chain reaction of a vector specific sequence in deoxyribonucleic acid (DNA) extracted from peripheral blood mononuclear cell (PBMC). |
| Cell cytokine levels and tumor biomarkers in peripheral blood and serous effusion (if present) | Day 0 - Day 730 | Blood samples and serous effusion (if present) were collected to measure cytokines IL-6, TNF-α, IL-8, IFN-γ, C-reactive protein (CRP), as well as ALPP concentration, Alpha-fetoprotein (AFP), Human chorionic gonadotropin (hCG), etc. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORQingzhu Jia, M.D.
Xinqiao Hospital
Outcome results
None listed