Back to resultsVaccine Therapy Plus Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma
Primary Purpose
Melanoma (Skin)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
aldesleukin
gp100 antigen
incomplete Freund's adjuvant
sargramostim
tetanus peptide melanoma vaccine
tyrosinase peptide
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma (Skin) focused on measuring stage III melanoma, stage IV melanoma, recurrent melanoma
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed stage III or IV melanoma gp100 positive tumor cells and/or tyrosinase positive tumor cells HLA type A1, A2, or A3 Measurable disease May have up to 3 brain metastases if all are less than 2 cm in diameter and are asymptomatic, and there is no mass effect or they have been treated successfully by surgical excision or by gamma knife radiation therapy PATIENT CHARACTERISTICS: Age: 18 to 79 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class II, III, or IV heart disease Other: No known or suspected allergy to any component of the vaccine No medical condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 months since prior growth factors At least 3 months since prior agents with putative immunomodulating activity (except nonsteroidal antiinflammatory agents) At least 1 year since other prior melanoma vaccinations Chemotherapy: At least 3 months since prior chemotherapy No concurrent chemotherapy Endocrine therapy: At least 3 months since prior corticosteroids No concurrent corticosteroids Radiotherapy: At least 3 months since prior radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 3 months since other prior investigational drugs or therapy At least 3 months since prior allergy desensitization injections At least 14 days since completion of acute treatment for a serious infection No concurrent allergy desensitization injections
Sites / Locations
- Cancer Center at the University of Virginia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Peptides pulsed on dendritic cells
Peptides in GMCSF-in-adjuvant
Arm Description
4 melanoma peptides pulsed on monocyte-derived dendritic cells
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
Outcomes
Primary Outcome Measures
Evaluation of Objective Clinical Response (CR/PR/SD)
The primary end point for this trial was clinical response. This was assessed by measurement of assessable metastatic deposits by CT, MRI, or direct measure of cutaneous deposits. Baseline tumor measurements used for assessment of clinical response were those obtained most immediately before the first vaccine administration and within 6 weeks of protocol entry. Measurements were made and reviewed by a multidisciplinary team. The original protocol defined tumor response on the basis of changes in cross-sectional area calculated as the product of two perpendicular measures. However, since the initiation of this study, the Response Evaluation Criteria in Solid Tumors Group (RECIST) system was employed as the current standard for clinical trials, in which response is based on changes in maximum cross-sectional dimensions. Computed tomography scans of clinical responders were reviewed again by a senior faculty radiologist not otherwise involved in the study.
Measure of Tumor-antigen-specific Immunity in Peripheral Blood Mononuclear Cells (PBMC) by Elispot Assay
Measure of Tumor-antigen-specific Immunity in Sentinel Immunized Node (SIN) by Elispot Assay
Secondary Outcome Measures
Full Information
NCT ID
NCT00003222
First Posted
November 1, 1999
Last Updated
December 18, 2014
Sponsor
University of Virginia
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00003222
Brief Title
Vaccine Therapy Plus Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma
Official Title
Phase II Trial for the Evaluation of the Efficacy of Vaccination With Synthetic Melanoma Peptides Either Pulsed on Dendritic Cells, or Administered With GM-CSF-in-Adjuvant, Plus Administration of Sustemic IL-2, in Patients With Advanced Melanoma.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
April 1998 (undefined)
Primary Completion Date
September 2003 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Virginia
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Vaccines made from melanoma cells may make the body build an immune response to and kill tumor cells. Colony-stimulating factors such as GM-CSF may increase the number of immune cells found in the bone marrow or peripheral blood. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. Combining vaccine therapy with GM-CSF and interleukin-2 may be kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of vaccines made from melanoma cells with or without GM-CSF followed by interleukin-2 in treating patients with stage III or stage IV melanoma.
Detailed Description
OBJECTIVES: I. Compare the effectiveness of vaccination with synthetic melanoma peptides pulsed on autologous dendritic cells versus vaccination with synthetic melanoma peptides plus sargramostim (GM-CSF) in decreasing tumor burden in patients with high risk melanoma (pulsed autologous dendritic cell arm closed 1/8/2001). II. Determine whether these regimens result in increased tumor specific immune responses as measured in vitro and in vivo. III. Determine whether these regimens stimulate T-cell responses in these patients.
OUTLINE: This is an open label study. Patients are included in treatment arm II only (arm I closed 1/8/2001): Arm I: Patients undergo leukapheresis to collect dendritic cells. Patients receive a mixture of synthetic melanoma peptides (gp100 antigen, tyrosinase, and tetanus peptides) pulsed on autologous dendritic cells IV and subcutaneously (SC). Arm II: Patients receive a mixture of synthetic melanoma peptides (gp100 antigen, tyrosinase, and tetanus peptides) and sargramostim (GM-CSF) emulsified in Montanide ISA-51 SC and intradermally. Patients receive vaccination during weeks 0, 1, 2, 4, 5, and 6 for a total of 6 doses and interleukin-2 SC daily on days 7-49. Patients receive 3 additional vaccinations at different sites not involved with the tumor concurrently with the first 3 vaccinations. Patients are evaluated at 8 weeks, 12 weeks, 6 months, 12 months, and 24 months.
PROJECTED ACCRUAL: A total of 27-54 patients will be accrued for this study within 2 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma (Skin)
Keywords
stage III melanoma, stage IV melanoma, recurrent melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Peptides pulsed on dendritic cells
Arm Type
Experimental
Arm Description
4 melanoma peptides pulsed on monocyte-derived dendritic cells
Arm Title
Peptides in GMCSF-in-adjuvant
Arm Type
Experimental
Arm Description
4 melanoma peptides administered as an emulsion with GM-CSF and Montanide ISA-51 adjuvant.
Intervention Type
Biological
Intervention Name(s)
aldesleukin
Other Intervention Name(s)
Interleukin-2
Intervention Description
Systemic subcutaneous delivery of low-dose IL-2.
Intervention Type
Biological
Intervention Name(s)
gp100 antigen
Intervention Type
Biological
Intervention Name(s)
incomplete Freund's adjuvant
Intervention Type
Biological
Intervention Name(s)
sargramostim
Intervention Type
Biological
Intervention Name(s)
tetanus peptide melanoma vaccine
Intervention Type
Biological
Intervention Name(s)
tyrosinase peptide
Primary Outcome Measure Information:
Title
Evaluation of Objective Clinical Response (CR/PR/SD)
Description
The primary end point for this trial was clinical response. This was assessed by measurement of assessable metastatic deposits by CT, MRI, or direct measure of cutaneous deposits. Baseline tumor measurements used for assessment of clinical response were those obtained most immediately before the first vaccine administration and within 6 weeks of protocol entry. Measurements were made and reviewed by a multidisciplinary team. The original protocol defined tumor response on the basis of changes in cross-sectional area calculated as the product of two perpendicular measures. However, since the initiation of this study, the Response Evaluation Criteria in Solid Tumors Group (RECIST) system was employed as the current standard for clinical trials, in which response is based on changes in maximum cross-sectional dimensions. Computed tomography scans of clinical responders were reviewed again by a senior faculty radiologist not otherwise involved in the study.
Time Frame
Weeks 0-6,12; Months 6,12 and 24
Title
Measure of Tumor-antigen-specific Immunity in Peripheral Blood Mononuclear Cells (PBMC) by Elispot Assay
Time Frame
Weeks 0-6,12; Months 6,12 and 24
Title
Measure of Tumor-antigen-specific Immunity in Sentinel Immunized Node (SIN) by Elispot Assay
Time Frame
Weeks 0-6,12; Months 6,12 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed stage III or IV melanoma gp100 positive tumor cells and/or tyrosinase positive tumor cells HLA type A1, A2, or A3 Measurable disease May have up to 3 brain metastases if all are less than 2 cm in diameter and are asymptomatic, and there is no mass effect or they have been treated successfully by surgical excision or by gamma knife radiation therapy
PATIENT CHARACTERISTICS: Age: 18 to 79 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class II, III, or IV heart disease Other: No known or suspected allergy to any component of the vaccine No medical condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 months since prior growth factors At least 3 months since prior agents with putative immunomodulating activity (except nonsteroidal antiinflammatory agents) At least 1 year since other prior melanoma vaccinations Chemotherapy: At least 3 months since prior chemotherapy No concurrent chemotherapy Endocrine therapy: At least 3 months since prior corticosteroids No concurrent corticosteroids Radiotherapy: At least 3 months since prior radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Other: At least 3 months since other prior investigational drugs or therapy At least 3 months since prior allergy desensitization injections At least 14 days since completion of acute treatment for a serious infection No concurrent allergy desensitization injections
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig L. Slingluff, MD
Organizational Affiliation
University of Virginia
Official's Role
Study Chair
Facility Information:
Facility Name
Cancer Center at the University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
14581425
Citation
Slingluff CL Jr, Petroni GR, Yamshchikov GV, Barnd DL, Eastham S, Galavotti H, Patterson JW, Deacon DH, Hibbitts S, Teates D, Neese PY, Grosh WW, Chianese-Bullock KA, Woodson EM, Wiernasz CJ, Merrill P, Gibson J, Ross M, Engelhard VH. Clinical and immunologic results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol. 2003 Nov 1;21(21):4016-26. doi: 10.1200/JCO.2003.10.005.
Results Reference
result
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Vaccine Therapy Plus Interleukin-2 in Treating Patients With Stage III or Stage IV Melanoma
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