Her2 and TGFBeta in Treatment of Her2 Positive Lung Malignancy - Full Text View

Sponsor:	Baylor College of Medicine
Collaborators:	Texas Children's Hospital The Methodist Hospital System Center for Cell and Gene Therapy
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00889954

Purpose

To determine the safety of one intravenous injections of autologous TGFBeta-resistant cytotoxic T lymphocytes (CTLs) directed to Epstein Barr virus (EBV) through their native receptor and HER2 through their chimeric antigen receptor (CAR) in patients with advanced HER2-positive lung tumors, the investigators will implement a Bayesian dose-finding phase-I trial design, called the modified continual reassessment method (mCRM). Each patient will receive one injection of the TGFBeta resistant HER2/EBV-specific CTLs according to the following dosing schedule:

Dose Level One: 1.5 x 10^7 cells/m^2

Dose Level Two: 4.5 x 10^7 cells/m^2

Dose Level Three: 1.2 x 10^8 cells/m^2

Each patient will be followed for 6 weeks after the CTL infusion for evaluation of dose limiting toxicity (DLT). For this trial, the maximum tolerated dose (MTD) is defined to be the dose which causes DLT in 20% of pts. The toxicity will be evaluated by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 3.0. Any toxicity that is irreversible or life threatening or non-hematologic Grade 3 or 4 considered to be primarily related to the CTL injection will be classified as DLT. All patients within a dose cohort should have completed the 6-week window after the CTL infusion for assessment of dose limiting toxicity prior to enrollment of patients into the next recommended dose level.

Condition	Intervention	Phase
Lung Malignancy	Genetic: Genetically modified T cells	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study
Official Title:	Administration of Her2 Chimeric Receptor and TGFbeta Dominant Negative Receptor (DNR) Expressing EBV Specific Lymphocytes for Subjects With Advanced Her2 Positive Lung Malignancy (HERCREEM)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

Determine safety of one IV injection of autologous TGFBeta-resistant CTLs directed to Epstein Barr virus (EBV) through their native receptor and HER2 through their chimeric antigen receptor (CAR) in patients with advanced HER2-positive lung cancers. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To compare the survival and the immune function of the TGFBeta-resistant and non resistant components of the infused CAR-CTL. [ Time Frame: 15 years ] [ Designated as safety issue: No ]
To assess the anti-tumor effects of the infused CAR-CTL. [ Time Frame: 15 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	May 2009
Estimated Study Completion Date:	July 2030
Estimated Primary Completion Date:	July 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Dose Level One: 1.5 x 10^7 cells/m^2: Experimental	Genetic: Genetically modified T cells Each patient will receive one injection of the TGFBeta resistant HER2/EBV-specific CTLs.Each pt will be followed for 6 weeks after the CTL infusion for evaluation of dose limiting toxicity (DLT). All pts within a dose cohort should have completed the 6-week window after the CTL infusion for assessment of dose limiting toxicity as defined below prior to enrollment of pts into the next recommended dose level.
Dose Level Two: 4.5 x 10^7 cells/m^2: Experimental	Genetic: Genetically modified T cells Each patient will receive one injection of the TGFBeta resistant HER2/EBV-specific CTLs.Each pt will be followed for 6 weeks after the CTL infusion for evaluation of dose limiting toxicity (DLT). All pts within a dose cohort should have completed the 6-week window after the CTL infusion for assessment of dose limiting toxicity as defined below prior to enrollment of pts into the next recommended dose level.
Dose Level Three: 1.2 x 10^8 cells/m^2: Experimental	Genetic: Genetically modified T cells Each patient will receive one injection of the TGFBeta resistant HER2/EBV-specific CTLs.Each pt will be followed for 6 weeks after the CTL infusion for evaluation of dose limiting toxicity (DLT). All pts within a dose cohort should have completed the 6-week window after the CTL infusion for assessment of dose limiting toxicity as defined below prior to enrollment of pts into the next recommended dose level.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The patient must meet the following eligibility inclusion criteria at the time of PROCUREMENT:

Diagnosis of HER2-positive lung cancer
Karnofsky/Lansky score of 50 or more
EBV seropositive
Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

The patient must meet the following eligibility criteria to be included for TREATMENT:

Diagnosis of HER2-positive lung cancer
EBV-seropositive
Recovered from the acute toxic effects of all prior chemotherapy at least a week before entering this study.
Normal ECHO (Left ventricular ejection fraction (LVEF) has to be with in normal, institutional limits)
Life expectancy 6 weeks or more
Karnofsky/Lansky score of 50 or more
Bilirubin 3x or less, AST 5x or less, Serum creatinine 2x upper limit of normal or less, Hgb 8.0 or more
Pulse oximetry 90% or more on room air
Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. Male partner should use a condom
Available autologous transduced EBV-specific cytotoxic T lymphocytes with 15% or more expression of HER2 CAR and 15% or more expression of TGFâ DNR with 10% or more dual positive, determined by flow-cytometry
Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria:

At time of Procurement:

1. Known HIV positivity

At time of Treatment:

Severe intercurrent infection
Known HIV positivity
Pregnant or lactating
History of hypersensitivity reactions to murine protein-containing products

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00889954

Contacts

Contact: Stephen Gottschalk, MD

832-824-4179

smgottsc@txccc.org

Locations

United States, Texas
The Methodist Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Stephen Gottschalk, MD 832-824-4179 smgottsc@txccc.org
Principal Investigator: Stepehen Gottschalk, MD

Sponsors and Collaborators

Baylor College of Medicine

Texas Children's Hospital

The Methodist Hospital System

Center for Cell and Gene Therapy

Investigators

Principal Investigator:

Stepehen Gottschalk, MD

Baylor College of Medicine/Texas Children's Hospital

More Information

No publications provided

Responsible Party:	Baylor College of Medicine/Texas Children's Hospital ( Stephen Gottschalk, MD )
Study ID Numbers:	24486 HERCREEM
Study First Received:	April 24, 2009
Last Updated:	May 29, 2009
ClinicalTrials.gov Identifier:	NCT00889954 History of Changes
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:

EBV+
Her2
Lung
TGFBeta
EBV positive

Additional relevant MeSH terms:

Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site

Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases

ClinicalTrials.gov processed this record on November 20, 2009