Her2 and TGFBeta Cytotoxic T Cells in Treatment of Her2 Positive Malignancy

NCT00889954 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 24486-HERCREEMHERCREEM
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

Patients have advanced stage cancer. This study is a gene transfer research study using special immune cells. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Investigators hope that both will work better together. Antibodies are proteins that protect the body from diseases caused from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients. T lymphocytes can kill tumor cells but there are normally not enough of them or they are not able to kill all the tumor cells. We have done research in which we have grown "extra" T lymphocytes. We have added genes to those T lymphocytes to help them to recognize tumor cells. Although the results have been promising, we are still doing more research in this area. Antibodies usually circulate in blood and are secreted by other cells of the immune system in response to the presence of germs or abnormal cells in the body. The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor 2). This antibody sticks to HER2-positive cancer cells because of a substance on the outside of these cells called HER2.

Conditions

HER2 Positive Malignancies

Keywords

EBV+; Her2; TGFBeta; EBV positive; HER 2 positive malignancy; cytotoxic T lymphocytes

Outcome Measures

Primary Outcomes (1)

• Number of Patients with dose limiting toxicity.

  Determine safety of one IV injection of autologous TGFBeta-resistant cytotoxic T cells (CTL) directed to Epstein Barr virus (EBV) through their native receptor and HER2 through their chimeric antigen receptor (CAR) in patients with advanced HER2- positive cancers.

  6 weeks

Secondary Outcomes (2)

• Area under the growth curves (AUC) over time for T cell frequencies.

  15 years

• Decrease in tumor after the CTL infusion

  15 years

Study Arms (1)

TGFBeta resistant HER2/EBV-CTLs

EXPERIMENTAL

The following dose levels will be evaluated: Dose Level 1: 1 x 10\^4 cells/m\^2 Dose Level 2: 3 x 10\^4 cells/m\^2 Dose Level 5: 1 x 10\^6 cells/m\^2 Dose Level 6: 3 x 10\^6 cells/m\^2 Dose Level 7: 1 x 10\^7 cells/m\^2 Dose Level 8: 3 x 10\^7 cells/m\^2 Dose Level 9:1 x 10\^8 cells/m\^2

Biological: TGFBeta resistant HER2/EBV-CTLs

Interventions

TGFBeta resistant HER2/EBV-CTLs BIOLOGICAL

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). Patients may receive up to six additional doses of the T cells at 6 to 12 weeks intervals.

Also known as: HER2-DNR EBV T cells

TGFBeta resistant HER2/EBV-CTLs

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of advanced stage\* or metastatic HER2-positive cancer (Immunohistochemistry or reverse transcription-polymerase chain reaction (RT-PCR) is used to determine HER2 positivity)
• Definitions of Malignancies and Advanced Stages:
• Breast ≥Stage IIIb Colon cancer ≥Stage IIIb Esophageal cancer ≥Stage IIIb Gastric carcinoma ≥Stage IIIb Head and Neck cancer Stage IV Lung cancer ≥Stage IIIb Pancreatic cancer Stage IV Prostate cancer Stage IV
• \*it is expected that the majority of patients who will be accrued on the protocol will have one of the HER2-positive malignancies listed in the table. If the patient's malignancy is not listed we will use ≥ Stage IIIb as the definition of advanced stage disease. If Stage IIIb is not part of the staging system for the individual tumor, Stage IV will be used.
• For World Health Organization grade III and IV brain tumors):patients will be eligible, who have recurrent or progressive disease after front line therapy.
• Karnofsky/Lansky score of 50 or more
• EBV seropositive
• Greater than or equal to 3 years old
• 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 advanced stage\* or metastatic HER2-positive cancer with disease progressed after receiving at least one prior systemic therapy. (Immunohistochemistry or RT-PCR is used to determine HER2 positivity) \*for definition refer to Table above.
• Greater than or equal to 3 years old.
• EBV-seropositive
• Recovered from the acute toxic effects of all prior chemotherapy at least a week before entering this study.
• Normal echocardiogram (Left ventricular ejection fraction (LVEF) has to be with in normal, institutional limits)

You may not qualify if:

• At time of Procurement:
• \. 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

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Camurati-Engelmann Syndrome

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Stepehen Gottschalk, MD

  Baylor College of Medicine - Texas Children's 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: Associate Professor Pediatric Hematology/Oncology Center for Cell and Gene Therapy

Study Record Dates

• First Submitted: April 24, 2009
• First Posted: April 29, 2009
• Study Start: May 1, 2009
• Primary Completion: July 1, 2015
• Study Completion: January 21, 2018
• Last Updated: September 18, 2018

Record last verified: 2018-09

Locations

US (2)