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

NCT03159819 | Unknown DMC

• 1 other identifier: CG4003
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Gastric Adenocarcinoma; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and tolerance

  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 Outcomes (1)

• Engraftment

  2 years

Other Outcomes (4)

• Anti-tumor responses to CAR-CLD18 T cell infusions

  2 years

• Anti-tumor responses to CAR-CLD18 T cell infusions

  2 years

• Anti-tumor responses to CAR-CLD18 T cell infusions

  2 years

Study Arms (1)

CAR-CLD18 T cells

EXPERIMENTAL

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

Interventions

CAR-CLD18 T Cells GENETIC

Dose escalation will be applied in this study.

Also known as: Claudin18.2-redirected Autologous Cells

CAR-CLD18 T cells

Eligibility Criteria

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

You may qualify if:

• Patients aged 18 - 70 with pathologically confirmed advanced gastric adenocarcinoma and pancreatic adenocarcinoma.
• Biopsy confirmation of Claudin18.2 positive.
• 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.
• 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.
• Expected survival after first dose of study drug \> 12 weeks.
• At least one measurable lesion (≥ 10 mm) for imaging assessment.
• ECOG scores 0 - 1.
• Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
• 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%
• Serum albumin (Alb) ≥ 30 g/L
• Serum lipase (LPS) and serum amylase \< 1.5 ULN
• Serum creatinine ≤ 1.5 ULN
• 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.
• Serum total bilirubin (TBIL) ≤ 1.5 ULN
• Prothrombin Time (PT): International Normalized Ratio (INR) \< 1.7. PT \< (ULN + 4) s

You may not qualify if:

• Patients with any of the following conditions are not eligible for the study.
• Pregnant or lactating women.
• HIV positive, HCV positive, HBV DNA copies ≥ 10\^3.
• Uncontrolled active infection.
• Allergic to immunotherapies and related drugs.
• Untreated brain metastases or having symptoms of brain metastases.
• Metastases to the lung: central tumor or multiple metastases.
• Patients with heart disease for which treatment is needed or with poorly controlled hypertension.
• Patients with unstable or active peptic ulcer or with alimentary tract hemorrhage.
• Patients with previous organ transplantation or in preparation for organ transplantation.
• Patients in need of anticoagulant treatment (e.g. warfarin or heparin).
• Patients in need of long-term antiplatelet treatment (aspirin, dosage \> 300 mg/d; clopidogrel, dosage \> 75 mg/d).
• Previous treatment with chemoradiotherapy and tumor-targeting drug which were conducted 4 weeks prior to the study (blood collection).
• 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.
• The judgment of investigators that the patient is not able to or not willing to follow the instructions of the protocol.

Sponsors & Collaborators

• Changhai Hospital: lead
• CARsgen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

Changhai Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Study Officials

• Xianbao Zhan, M.D.

  Changhai Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xianbao Zhan, M.D.

CONTACT

86-021-31161441; zhanxianbao@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending physician

Study Record Dates

• First Submitted: May 11, 2017
• First Posted: May 19, 2017
• Study Start: April 1, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2021
• Last Updated: March 12, 2018

Record last verified: 2018-03

Locations

CN (1)