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A Phase I Study of Active Immunotherapy With CAP-1 (6D) and CMVpp65 Peptide-Pulsed, Autologous Dendritic Cells Produced in the Aastromreplicell Cell Production System in Patients With Stage IV CEA Expressing Malignancies


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of Active Immunotherapy With CAP-1 (6D) and CMVpp65 Peptide-Pulsed, Autologous Dendritic Cells Produced in the Aastromreplicell Cell Production System in Patients With Stage IV CEA Expressing Malignancies


OBJECTIVES:

- Determine the safety and feasibility of administering 1 or 2 courses of vaccination
with carcinoembryonic antigen peptide 1-6D (CAP 1-6D)- and CMV pp65 peptide-pulsed
autologous dendritic cells in patients with refractory stage IV CEA-expressing
malignancies.

- Determine the ability of this regimen to induce CAP 1-6D- and CMV pp65-specific T cells
in these patients.

- Determine the antitumor effect of this regimen, in terms of progression-free survival,
of these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients undergo leukapheresis and collection of peripheral blood mononuclear cells from
which dendritic cells (DC) are generated and pulsed with carcinoembryonic antigen peptide
1-6D (CAP 1-6D) and CMV pp65 peptide. Patients are assigned to 1 of 2 vaccination cohorts.

- Cohort I: Patients receive vaccination with CAP 1-6D-pulsed DC and CMV pp65
peptide-pulsed DC subcutaneously and intradermally every 3 weeks for a total of 4
vaccinations.

- Cohort II: Patients receive vaccinations as in cohort I every 3 weeks for a total of 8
vaccinations.

For both cohorts, a safe dose of the vaccine is defined as the dose at which no more than 1
of 6 patients experiences unacceptable toxicity.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 12 patients (6 per cohort) will be accrued for this study
within 24 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed malignancy that is refractory to standard therapy known to
have a survival benefit

- Stage IV disease

- Carcinoembryonic antigen (CEA)-expressing tumor, as evidenced by 1 of the following:

- Immunohistochemistry with at least 50% of the tumor with at least moderate
intensity of staining

- Peripheral blood CEA greater than 2.5 mg/dL

- Tumor known to be universally CEA positive (i.e., colon or rectal cancer)

- HLA-A201 positive

- Measurable disease*

- At least 1 unidimensionally measurable lesion at least 20 mm by conventional
techniques OR at least 10 mm by spiral CT scan NOTE: *Histologic or cytologic
confirmation is not required for measurable disease restricted to a solitary
lesion

- Received at least 1 prior standard chemotherapy regimen known to have a survival
benefit

- Previously resected brain metastases allowed provided CT scan or MRI was performed
within the past month and shows no metastasis

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 70-100%

Life expectancy

- More than 6 months

Hematopoietic

- WBC at least 3,000/mm^3

- Hemoglobin at least 9 g/dL (transfusions or red blood cell growth factors [e.g.,
epoetin alfa] allowed)

- Platelet count at least 100,000/mm^3

Hepatic

- Bilirubin less than 2.0 mg/dL (unless patient has Gilbert's disease)

- SGOT/SGPT less than 1.5 times upper limit of normal

- No hepatic disease that would preclude study participation

- No viral hepatitis (including chronic hepatitis) by hepatitis B surface antigen and
hepatitis C serology

Renal

- Creatinine less than 2.5 mg/dL

- No urinary tract infection

Cardiovascular

- No New York Heart Association class III or IV heart disease

Immunologic

- No history of autoimmune disease, including any of the following:

- Inflammatory bowel disease

- Systemic lupus erythematosus

- Ankylosing spondylitis

- Scleroderma

- Multiple sclerosis

- No active acute or chronic infection

- HIV negative

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other serious chronic or acute illness that would preclude study participation

- No medical or psychological impediment that would preclude study compliance

- No other malignancy within the past 5 years except nonmelanoma skin cancer,
controlled carcinoma in situ of the cervix, or controlled superficial bladder cancer

- No allergy to study vaccine components

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 4 weeks since prior immunotherapy

- No other concurrent immunotherapy

Chemotherapy

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy

- No concurrent chemotherapy

Endocrine therapy

- At least 6 weeks since prior steroid therapy (except steroids administered as
premedication for chemotherapy or contrast-enhanced studies)

- Concurrent hormonal therapy allowed for patients with breast cancer

- No concurrent steroid therapy

Radiotherapy

- At least 4 weeks since prior radiotherapy

- No concurrent radiotherapy

Surgery

- Not specified

Other

- Recovered from prior therapy

- At least 4 weeks since prior investigational therapy

- At least 4 weeks since other prior therapy

- Any number of prior therapies are allowed

- Concurrent bisphosphonates allowed for bone metastases

- No concurrent immunosuppressive therapy (e.g., azathioprine or cyclosporine)

- No other concurrent experimental therapies

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Safety

Outcome Description:

The safety and feasibility of administering one cycle of CAP-1(6D) and CMV pp65 peptide-pulsed, matured, autologous human DC produced by the AastromReplicell™ Cell Production System

Outcome Time Frame:

12 months

Safety Issue:

Yes

Principal Investigator

Herbert K. Lyerly, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Duke Cancer Institute

Authority:

United States: Federal Government

Study ID:

4180

NCT ID:

NCT00057915

Start Date:

September 2003

Completion Date:

September 2006

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific

Name

Location

Duke Comprehensive Cancer Center Durham, North Carolina  27710