Anti-ALPP CAR-T Cells Immunotherapy for Ovarian and Endometrial Cancer

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the safety and efficacy of anti-ALPP chimeric antigen receptor (CAR)-modified T (CAR-T) cells in treating patients with ALPP-positive metastatic ovarian and endometrial cancer.

Detailed Description
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Primary Objectives: To evaluate the number of ALPP-positive participants with treatment-related adverse events as assessed by CTCAE v4.0 after infusion with anti-ALPP CAR-T cells. Secondary Objectives: The number of patients experience objective response from anti-ALPP CAR-T cells treatment To evaluate the progression-free survival (PFS) of anti-ALPP CAR-T cells in patients with ALPP-positive patients. The number and percent of ALPP-CART cells in peripheral blood from ALPP-positive patients at 6 months after infusion

Official Title
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A Single-Arm, Single-Center, Open-Label Pilot Study of Anti-ALPP CART-cells in Patient With Alkaline Phosphatase, Placental (ALPP)-Positive Metastatic Ovarian and Endometrial Cancer.

Conditions
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Ovarian Cancer, Endometrial Cancer

Intervention / Treatment
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* Drug: Retroviral vector-transduced autologous T cells to express anti-ALPP CARs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Expected to survive more than 3 months PS 0-2 Immunohistochemistry was confirmed to be mesothelin positive ALPP (higher than 50%) Patients with no curative regimen to receive WBC>3.5×1e+9/L,Hb>90g/L,PLT>75×1e+9/L HBV DNA copy number less than 100/ml ALT≤5ULN, AST≤5ULN, TB≤1.5ULN, ALB≥35g/L Understand this test and have signed informed consent Exclusion Criteria: Autoimmune diseases, or any uncontrolled active disease that hinders participation in the trial Decompensated liver cirrhosis, liver function Child-pugh C grade Portal vein tumor thrombus, arterial portal fistula, hepatic arteriovenous Long-term use of immunosuppressive agents after organ transplantation Screening indicated that the target cell transfection rate was less than 30% Invasive pulmonary embolism, deep venous thrombosis, or other major arterial / venous thromboembolic events occurred 30 days or 30 days prior to randomization Subjects had an active or uncontrollable infection requiring systemic therapy 14 days or 14 days prior to randomization Pregnant or lactating subjects In the opinion of the investigator, the presence of a medical history or a history of mental state may increase the number of subjects associated with the risk factors associated with the study or study drug administration Subjects who have signed a written consent or who are in compliance with the study procedure; or who are unwilling or unable to comply with the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CART treatment<br>Cyclophosphamide will be administered at dose of 20mg/kg for 1 day and then fludarabine will be given for the next 3 days with 35mg/m2 and then the CAR-T cells will be administered | Drug: Retroviral vector-transduced autologous T cells to express anti-ALPP CARs<br>* Cyclophosphamide will be administered at dose of 20mg/kg for 1 day and then fludarabine will be given for the next 3 days with 35mg/m2 and then the CAR-T cells will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients suffering treatment-related AE | To evaluate the number of ALPP-positive participants with treatment-related adverse events as assessed by CTCAE v4.0 after infusion with anti-ALPP CAR-T cells. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate to ALPP-CART infusion | The number of patients experience objective response from anti-ALPP CAR-T cells treatment | Eight weeks | 
| Progression-free survival to ALPP-CART infusion | To evaluate the progression-free survival (PFS) of anti-ALPP CAR-T cells in patients with mesothelin-positive advanced ovarian carcinoma. | 6 months | 
| Number of peripheral CAR-T after infusion | The number of ALPP-CART cells in peripheral blood from ALPP-positive patients at 6 months after infusion | 6 months |