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
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
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
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
North Carolina
-
Durham, North Carolina, United States, 27705
- Duke Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: CEA peptide 1-6D
CAP-1(6D) peptide-pulsed, matured, autologous human DC produced by the AastromReplicell™ Cell Production System
|
CAP-1(6D) peptide-pulsed, matured, autologous human DC produced by the AastromReplicell™ Cell Production System
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Safety
Time Frame: 12 months
|
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
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Immune response
Time Frame: 12 weeks
|
The ability of the epitope pulsed DC to induce CAP-1(6D) and CMV pp65-specific T cells
|
12 weeks
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Study record dates
Study Major Dates
Study Start
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimate)
First Posted
Study Record Updates
Last Update Posted (Estimate)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
Other Study ID Numbers
- 4180 (Other Identifier: Duke IRB)
- 5910 (Other Grant/Funding Number: NCI)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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