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A Phase I Study of Infusion of HER-2/Neu Specific T Cells in Patients With Advanced Stage HER-2/Neu Expressing Cancers Who Have Received a HER-2/Neu Vaccine


Phase 1
18 Years
N/A
Open (Enrolling)
Both
HER2-positive Breast Cancer, Recurrent Breast Cancer, Recurrent Non-small Cell Lung Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Ovarian Germ Cell Tumor, Stage IV Breast Cancer, Stage IV Non-small Cell Lung Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Ovarian Germ Cell Tumor

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Trial Information

A Phase I Study of Infusion of HER-2/Neu Specific T Cells in Patients With Advanced Stage HER-2/Neu Expressing Cancers Who Have Received a HER-2/Neu Vaccine


PRIMARY OBJECTIVES:

I. To assess the feasibility of expanding HER2 specific T cells ex vivo for infusion into
subjects who have advanced HER2 overexpressing cancer.

II. To assess the toxicity associated with infusing autologous HER2 specific T cells into
patients using either a single dose of cyclophosphamide or ONTAK (denileukin diftitox) prior
to T cell infusion.

SECONDARY OBJECTIVES:

I. To investigate to what extent HER2 specific T cell immunity can be boosted in individuals
treated with a single dose of cyclophosphamide of ONTAK followed by infusion of autologous
HER2 specific T cells.

II. To investigate the potential anti-tumor effects of HER2 specific T cells in patients
with HER2 overexpressing advanced-stage cancers.

III. To evaluate how long tumor antigen specific T cell immune augmentation persists in vivo
after a single dose of cyclophosphamide or ONTAK followed by infusion of autologous HER2
specific T cells.

OUTLINE: This is a dose-escalation study of ex vivo-expanded HER2-specific T cells. Patients
are assigned to 1 of 2 treatment groups.

GROUP A: Patients receive low-dose cyclophosphamide intravenously (IV) on day -1 and 3
escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on
days 1, 10, and 20.

GROUP B: Patients receive ONTAK (denileukin diftitox) IV over 1 hour on day -1 and 3
escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on
days 1, 10, and 20.

After completion of study treatment, patients are followed periodically.


Inclusion Criteria:



- Patients with progressive HER2/neu overexpressing metastatic breast, ovarian, or
non-small cell lung cancer not considered curable by conventional therapies,
including trastuzumab

- Extra-skeletal disease that can be accurately measured >= 10 mm by standard
imaging techniques that can include but not limited to computed tomography (CT),
positron emission tomography (PET), magnetic resonance imaging (MRI)

- Skeletal or bone-only disease which is measurable by Fludeoxyglucose F 18 (FDG)
PET imaging will also be allowed

- Patients with ovarian cancer may have measurable disease; however, their only
indication of progression may be an abnormal CA-125

- Patients must have documented HER-2/neu overexpression in their tumor (either primary
or metastasis) as was required per the eligibility criteria of their original
vaccination protocol

- Patients must have received HER2-specific vaccinations while enrolled on a HER2
vaccine protocol approved at the University of Washington Human Subjects Division

- Patients must have undergone leukapheresis after vaccination through a protocol
approved at the University of Washington Human Subjects Division and have product
stored for clinical use

- Subjects must have a Performance Status Score (Zubrod/Eastern Cooperative Oncology
Group [ECOG] Scale) = 0 or 1

- Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal
therapy and/or bisphosphonate therapy

- Patients on trastuzumab and/or lapatinib must have adequate cardiac function as
demonstrated by multi gated acquisition (MUGA) scan or echocardiogram (ECHO)
within 90 days of eligibility determination

- Patients must be off all immunosuppressive treatments, and/or systemic steroid
therapy, for at least 14 days prior to initiation of study treatment

- Patients must be off chemotherapy and trastuzumab for at least 1 week prior to the
first infusion of T cells

- Men and women of reproductive ability must agree to contraceptive use during the
study and for one month after the final T cell infusion

- Patients with a history of brain metastases must have a stable head imaging study
within 30 days of enrollment

- White blood cells (WBC) >= 3000/mm^3

- Absolute neutrophil count (ANC) >= 1000/mm^3

- Hemoglobin (Hgb) >= 10 mg/dl

- Platelets >= 75,000mm^3

- Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min

- Total bilirubin =< 2.5 mg/dl

- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3
times ULN

Exclusion Criteria:

- Concurrent enrollment in other treatment studies

- Patients with any of the following cardiac conditions:

- Symptomatic restrictive cardiomyopathy

- Unstable angina within the last 4 months prior to enrollment

- New York Heart Association functional class III-IV heart failure on active
treatment

- Patients with any clinically significant autoimmune disease uncontrolled with
treatment

- Pregnant or breast-feeding women

- Known history of hypersensitivity to diphtheria toxin or interleukin (IL)-2 (only for
subjects enrolled in Group B)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility of expanding HER2 specific T cells ex vivo to achieve a target T cell expansion of 1x10^10 HER2 specific T cells

Outcome Description:

The procedure will be defined as feasible if the minimum target expansion of HER2 specific T cells is achieved in 2/3 expansions in 4/5 subjects within an arm.

Outcome Time Frame:

Up to day 40

Safety Issue:

No

Principal Investigator

Mary Disis

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

6223

NCT ID:

NCT00228358

Start Date:

June 2003

Completion Date:

Related Keywords:

  • HER2-positive Breast Cancer
  • Recurrent Breast Cancer
  • Recurrent Non-Small Cell Lung Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Ovarian Germ Cell Tumor
  • Stage IV Breast Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Stage IV Ovarian Epithelial Cancer
  • Stage IV Ovarian Germ Cell Tumor
  • Breast Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Germinoma
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109