Vaccine Therapy in Treating Patients With Refractory Stage IV Cancer

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

RATIONALE: Vaccines made from a person's white blood cells mixed with peptides may make the body build an immune response to kill cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with refractory stage IV cancer.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Biological: CEA peptide 1-6D

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CEA peptide 1-6D; CAP-1(6D) peptide-pulsed, matured, autologous human DC produced by the AastromReplicell™ Cell Production System	Biological: CEA peptide 1-6D; CAP-1(6D) peptide-pulsed, matured, autologous human DC produced by the AastromReplicell™ Cell Production System; Other Names: carcinoembryonic antigen peptide 1-6D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	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	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response	The ability of the epitope pulsed DC to induce CAP-1(6D) and CMV pp65-specific T cells	12 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: April 7, 2003
• First Submitted That Met QC Criteria: April 8, 2003
• First Posted (Estimate): April 9, 2003

Study Record Updates

• Last Update Posted (Estimate): September 8, 2014
• Last Update Submitted That Met QC Criteria: September 4, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Other Study ID Numbers: 4180 (Other Identifier: Duke IRB); 5910 (Other Grant/Funding Number: NCI)