Vaccine Therapy in Treating Patients With Refractory Stage IV Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: CEA peptide 1-6D


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific