ALPP CAR-T Cells for ALPP-Positive Advanced Solid Tumors

NCT06556108 | Completed Phase 1

• 1 other identifier: XQDC20191101
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity or Maximum Tolerated Dose (MTD)

  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.

  Day 28 post-initial ALPP CAR-T infusion

• Overall response rate

  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).

  Day 0 - Day 730

• Treatment-related adverse events as assessed by CTCAE v5.0

  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.

  Day 0 - Day 730

Secondary Outcomes (5)

• Duration of response

  Day 0 - Day 730

• Progression free survival

  Day 0 - Day 730

• Overall survival

  Day 0 - Day 730

• Expansion and persistence of ALPP CAR-T cells in peripheral blood or serous effusion (if present)

  Day 0 - Day 730

• Cell cytokine levels and tumor biomarkers in peripheral blood and serous effusion (if present)

  Day 0 - Day 730

Study Arms (1)

Arm 1

EXPERIMENTAL

This clinical study consists of 4 dose groups, with dose groups 1 and 2 using an accelerated titration dose escalation method, and dose groups 3 and 4 using a "3+3" dose escalation method. Interventions: Biological: CAR-T cells Drug: Fludarabine Drug: Cyclophosphamide

Biological: ALPP CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

ALPP CAR-T cells BIOLOGICAL

T cells genetically engineered with a CAR targeting ALPP (ALPP CAR) that display specific reactivity against ALPP target cells

Arm 1

Fludarabine DRUG

Part of the non-myeloablative lymphocyte-depleting preparative regimen.

Arm 1

Cyclophosphamide DRUG

Part of the non-myeloablative lymphocyte-depleting preparative regimen.

Arm 1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand and sign the Informed of Consent Document. Be willing to follow the procedure and protocol of the clinical trial;
• Age 18-70 (including boundary value), both male and female;
• Expected life span is more than 3 months from the date of signing the informed consent;
• ECOG score 0-1;
• Metastatic or recurrent solid tumors confirmed by histopathology;
• Refractory to standard treatment evaluated by radiological assessment;
• Be able provide fresh or preserved tissue specimen;
• At least 1 measurable lesion (according to RECIST 1.1);
• ALPP expression positivity determined by IHC；
• The organ marrow function of the subjects meets the following requirements:
• Marrow function：ANC≥ 1.5×109/L; PLT count≥ 75×109/L; HGB≥ 90 g/L;
• 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;
• 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);
• Renal function: Serum Creatinine (Cr)≤ 1.5 times ULN or Creatinine Clearance Rate (CrCl) ≥ 60ml/min;
• Cardiac function: Left Ventricular Ejection Fractions (LVEF)≥45%;

You may not qualify if:

• Be able to understand and sign the Informed of Consent Document. Be willing to follow the procedure and protocol of the clinical trial;
• Age 18-70 (including boundary value), both male and female;
• Expected life span is more than 3 months from the date of signing the informed consent;
• ECOG score 0-1;
• Metastatic or recurrent solid tumors confirmed by histopathology;
• Refractory to standard treatment evaluated by radiological assessment;
• Be able provide fresh or preserved tissue specimen;
• At least 1 measurable lesion (according to RECIST 1.1);
• ALPP expression positivity determined by IHC；
• The organ marrow function of the subjects meets the following requirements:
• Marrow function：ANC≥ 1.5×109/L; PLT count≥ 75×109/L; HGB≥ 90 g/L;
• 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;
• 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);
• Renal function: Serum Creatinine (Cr)≤ 1.5 times ULN or Creatinine Clearance Rate (CrCl) ≥ 60ml/min;
• Cardiac function: Left Ventricular Ejection Fractions (LVEF)≥45%;

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead

Study Sites (1)

Department of Hematology, Xinqiao Hospital

Chongqing, Chongqing Municipality, 400037, China

Location

MeSH Terms

Interventions

fludarabine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Qingzhu Jia, M.D.

  Xinqiao Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: February 10, 2022
• First Posted: August 15, 2024
• Study Start: January 1, 2018
• Primary Completion: January 30, 2025
• Study Completion: July 30, 2025
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)