Anti-ALPP CAR-T Cells Immunotherapy for Advanced Solid Tumors

Phase 1

Recruiting

• Conditions: Solid Tumors
• Interventions: Drug: Retroviral vector-transduced autologous T cells to express anti-ALPP CARs

• Registration Number: NCT04627740
• Lead Sponsor: Xinqiao Hospital of Chongqing

Brief Summary

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 Advanced Solid Tumors.

Detailed Description

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

Study Timeline

• Study First Submitted: 2020-11-05
• Study First Submitted QC: 2020-11-11
• Study First Posted: 2020-11-13
• Study Start: 2020-12-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-22
• Last Update Posted: 2024-10-23
• Primary Completion: 2024-12-31
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CART treatment	Retroviral vector-transduced autologous T cells to express anti-ALPP CARs	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

Primary Outcome Measures

Name	Time	Method
Number of patients suffering treatment-related AE	1 year	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 Outcome Measures

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

Trial Locations

Locations (1)

Department of Oncology, Xinqiao Hospital; 🇨🇳 ChongQing, Chongqing, China