Clinical Study of CAR-CLD18 T Cells in Patients With Advanced Gastric Adenocarcinoma and Pancreatic Adenocarcinoma

NCT ID: NCT03159819

Last Updated: 2018-03-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-01

Study Completion Date

2021-12-31

Brief Summary

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A single arm, open-label pilot study is designed to determine the safety, tolerability and engraftment of CAR-CLD18 T cells in patients with advanced gastric adenocarcinoma and pancreatic adenocarcinoma.

Detailed Description

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For patients with gastric adenocarcinoma who have not been cured with first line chemotherapy, and who are not willing to undergo second line chemotherapy after the failure of first line chemotherapy while there are no effective therapies for their unmet medical needs known at this time, and for patients with advanced/metastatic pancreatic adenocarcinoma which has relapsed after surgery or for which there is no surgical indication, who have not been cured with or refused to receive other standard regimens, single or multiple doses of CAR-CLD18 T cells will be given to observe safety and efficacy of CAR-CLD18 T cells.

Primary objectives:

Determine the safety, tolerability and cytokinetics of the autologous T cells transduced with anti-Claudin18.2 lentiviral vector in patients with gastric adenocarcinoma and pancreatic adenocarcinoma.

Secondary objectives:

Make a preliminary evaluation on the efficacy of CAR-CLD18 T cells in patients with gastric adenocarcinoma and pancreatic adenocarcinoma with the following parameters:

Time of tumor progression (TTP);

Disease Control Rate (DCR);

Objective Remission Rate (ORR);

Overall Survival (OS).

Conditions

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Advanced Gastric Adenocarcinoma Pancreatic Adenocarcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CAR-CLD18 T cells

Autologous T Cells with a Claudin18.2-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection.

Lymphodepletion conditioning regimen will be applied prior to CAR-CLD18 T cell infusion.

Group Type EXPERIMENTAL

CAR-CLD18 T Cells

Intervention Type GENETIC

Dose escalation will be applied in this study.

Interventions

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CAR-CLD18 T Cells

Dose escalation will be applied in this study.

Intervention Type GENETIC

Other Intervention Names

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Claudin18.2-redirected Autologous Cells

Eligibility Criteria

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Inclusion Criteria

1. Patients aged 18 - 70 with pathologically confirmed advanced gastric adenocarcinoma and pancreatic adenocarcinoma.
2. Biopsy confirmation of Claudin18.2 positive.
3. Patients with advanced gastric adenocarcinoma who have not been cured with second line chemotherapy, and who are not willing to undergo second line chemotherapy after the failure of first line chemotherapy. (1) Failure of treatment is defined as disease progression, recurrence or metastatic disease, or intolerable toxicities occurred after treatment. (2) Each line of treatment during the period of disease progression includes one or more chemotherapy drugs which are administered for not less than one cycle or even longer. Neoadjuvant/adjuvant therapy can be applied at an earlier stage of treatment. If patient has developed recurrence or metastatic disease within 24 weeks of neoadjuvant/adjuvant therapy, it is considered as one line of systemic chemotherapy. (3) Therapies that can be performed at an earlier stage are chemotherapy in conjunction with molecular targeted drugs.
4. Patients with advanced/metastatic pancreatic adenocarcinoma which has relapsed after surgery or for which there is no surgical indication, who have not been cured with or refused to receive other standard regimens.
5. Expected survival after first dose of study drug \> 12 weeks.
6. At least one measurable lesion (≥ 10 mm) for imaging assessment.
7. ECOG scores 0 - 1.
8. Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
9. White blood cells (WBCs) ≥ 2.5×10\^9/L Platelets (PLT) ≥ 100×10\^9/L Hemoglobin, Blood (Hb) ≥ 9.0 g/dL MID ≥ 1.5×10\^9/L Lymphocyte (LY) ≥ 0.47×10\^9/L LY% ≥ 15%
10. Serum albumin (Alb) ≥ 30 g/L
11. Serum lipase (LPS) and serum amylase \< 1.5 ULN
12. Serum creatinine ≤ 1.5 ULN
13. Alanine aminotransferase (ALT) ≤ 2.5 ULN Aspartate aminotransferase (AST) ≤ 2.5 ULN If osseous metastasis or liver metastasis is developed and alkaline phosphatase (ALP) \> 2.5 ULN, ALT and AST \< 1.5 ULN.
14. Serum total bilirubin (TBIL) ≤ 1.5 ULN
15. Prothrombin Time (PT): International Normalized Ratio (INR) \< 1.7. PT \< (ULN + 4) s

All test results should be within their normal ranges, and the patient is not receiving continuous supportive care.

Exclusion Criteria

* Patients with any of the following conditions are not eligible for the study.

1. Pregnant or lactating women.
2. HIV positive, HCV positive, HBV DNA copies ≥ 10\^3.
3. Uncontrolled active infection.
4. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
5. Allergic to immunotherapies and related drugs.
6. Untreated brain metastases or having symptoms of brain metastases.
7. Metastases to the lung: central tumor or multiple metastases.
8. Patients with heart disease for which treatment is needed or with poorly controlled hypertension.
9. Patients with unstable or active peptic ulcer or with alimentary tract hemorrhage.
10. Patients with previous organ transplantation or in preparation for organ transplantation.
11. Patients in need of anticoagulant treatment (e.g. warfarin or heparin).
12. Patients in need of long-term antiplatelet treatment (aspirin, dosage \> 300 mg/d; clopidogrel, dosage \> 75 mg/d).
13. Previous treatment with chemoradiotherapy and tumor-targeting drug which were conducted 4 weeks prior to the study (blood collection).
14. Patients have undertaken major surgeries or have been badly injured 4 weeks before the study (blood collection), or will undertake major surgeries during the study.
15. The judgment of investigators that the patient is not able to or not willing to follow the instructions of the protocol.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CARsgen Therapeutics Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Changhai Hospital

OTHER

Sponsor Role lead

Responsible Party

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Bin Wang

Attending physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Xianbao Zhan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Changhai Hospital

Locations

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Changhai Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xianbao Zhan, M.D.

Role: CONTACT

86-021-31161441

Facility Contacts

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Bin Wang, Dr.

Role: primary

86-021-31161448

Other Identifiers

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CG4003

Identifier Type: -

Identifier Source: org_study_id

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