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

March 8, 2018 updated by: Bin Wang, Changhai Hospital

Clinical Study of Redirected Autologous T Cells With a Claudin18.2-targeted Chimeric Antigen Receptor in Patients With Advanced Gastric Adenocarcinoma and Pancreatic Adenocarcinoma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200433
        • Recruiting
        • Changhai Hospital
        • Contact:
        • Principal Investigator:
          • Xianbao Zhan, M.D.
        • Sub-Investigator:
          • Bin Wang, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 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.
Genetic: CAR-CLD18 T Cells
Dose escalation will be applied in this study.
Other Names:
  • Claudin18.2-redirected Autologous Cells

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and tolerance
Time Frame: 24 weeks

During the trial conduction, especially within the 24 weeks of treatment phase when CAR-CLD18 T cell administered, all adverse events (including laboratory abnormality and clinical events) will be closely monitored, and all ≥ grade 3 adverse events per CTCAE (v 3.0) will be recorded, including but not limited to the toxicities potentially suspected to relate to infusion procedures and/or CAR-CLD18 T cell therapy as listed below:

  • Fever
  • Chills
  • Nausea, vomiting and other gastrointestinal symptoms
  • Fatigue
  • Hypotension
  • Respiratory distress
  • Tumor lysis syndrome
  • Cytokine release syndrome
  • Neutropenia, thrombocytopenia
  • Liver and kidney dysfunction
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Engraftment
Time Frame: 2 years
Duration of in vivo survival of CAR-CLD18 T cells is defined as "engraftment". The primary engraftment endpoint is the number of DNA vector copies per mL blood of CAR-CLD18 T cells at regular intervals through week 4 following the initial infusion. Q-PCR for CAR-CLD18 T vector sequences will be performed until any 2 sequential tests are negative, documented as engraftment and persistence of CAR-CLD18 T cells.
2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Anti-tumor responses to CAR-CLD18 T cell infusions
Time Frame: 2 years
Disease Control Rate (DCR)
2 years
Anti-tumor responses to CAR-CLD18 T cell infusions
Time Frame: 2 years
Progression-free Survival (PFS)
2 years
Anti-tumor responses to CAR-CLD18 T cell infusions
Time Frame: 2 years
Time of Tumor Progression (TTP)
2 years
Anti-tumor responses to CAR-CLD18 T cell infusions
Time Frame: 2 years
Overall Survival (OS)
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Changhai Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
CARsgen Therapeutics Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xianbao Zhan, M.D., Changhai Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2017

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2019

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 11, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 17, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 19, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 12, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CG4003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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