Melanoma
Conditions
Keywords
melanoma, recurrent, metastatic
Brief summary
This clinical trial is to determine if the addition of a standard of care drug, interferon-alfa 2b (IFN), with an investigation vaccine will have any affect on the immune system and/or your cancer. The investigational vaccine will be made with genes that are specific to melanoma and will be given intradermally (i.d.) every two weeks for a total of 3 vaccines. After the vaccines, subjects will be randomized to either receive a boost of high dose IFN or no boost. IFN will be administered intravenously (into a vein) for 5 consecutive days (Monday through Friday) every week for 4 weeks. Administration will begin approximately 30 days (± 7 days) after the 3rd vaccine. The first dose of IFNα2b may begin within 10 business days of randomization. All subsequent procedure dates for Group A will be based on the date of the first dose of IFNα2b.
Detailed description
This is a Phase I, single site study to evaluate the immunological effects of autologous DC transduced with the MART-1, tyrosinase and MAGE-A6 (melanoma associated antigens, MAA) genes in 30 subjects with recurrent, unresectable stage III, IV metastatic melanoma (M1a, M1b, M1c). AdVTMM2-transduced DC, 10e7, will be given intradermally (i.d.) every two weeks for a total of 3 vaccines. After the DC vaccines, subjects will be randomized to either receive a boost of high dose IFNa2b or no boost. Subjects randomized to receive the IFNa2b boost will receive Interferon-a2b, 20 MU/m2/d (rounded to the nearest 1 million units) administered intravenously for 5 consecutive days (Monday through Friday) every week for 4 weeks (induction). Administration will begin approximately 30 days (± 7 days) after the 3rd vaccine. The first dose of IFNα2b may begin within 10 business days of randomization. All subsequent procedure dates for Group A will be based on the date of the first dose of IFNα2b.. The end-points of this study are local and systemic toxicity, immunological response, generation of determinant spreading and anti-tumor immunity, and clinical response.
Interventions
BIOLOGICALDC Vaccine + IFN
Vaccine: The dose target is 1x10e7 AdVTMM2/DC per intradermal injection, or lower dose per sponsor's discretion. IFN: 20 MU/m²/d (rounded to the nearest 1.0 million unit) administered IV x 5 consecutive days out of 7 (M-F) every week x 4 weeks.
BIOLOGICALAdVTMM2/DC Vaccination
Vaccine: The dose target is 1x10e7 AdVTMM2/DC per intradermal injection.If cell counts are below the target, as few as 5x10e6 AdVTMM2/DC may be administered. However, at the discretion of the sponsor and/or the treating physician, a lower dose of DC that fulfills all of the other criteria for release may be administered on a case by case basis. If this occurs a dose exception form will be completed by the IMCPL, signed by the treating physician and filed in the subjects research records.
Sponsors
National Cancer Institute (NCI)
Lisa H. Butterfield, Ph.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability and willing to give consent * Patients age 18 and older with recurrent, inoperable stage III, IV, M1a, b or c melanoma (any tumor thickness and any number of lymph node involvement, and in-transit metastases, or distant metastases) (AJCC). Previously treated with any form of therapy (including chemotherapy, radiation therapy, immunotherapy or surgery) for either metastatic, relapsed, or primary melanoma are eligible for this trial, provided the previous treatment was completed \> 30 days prior to enrollment. * Patients should have at least 2 subcutaneous, intracutaneous, and accessible tumor deposits, lymph node or other site available for biopsy purposes. * Both men and women may be enrolled. Premenopausal females must have a negative pregnancy test prior to treatment and lactating females will have to discontinue breast feeding to be eligible. * ECOG Performance Status of 0 or 1. * No previous evidence of class 3 or greater New York Heart Association cardiac insufficiency or coronary artery disease. * No previous evidence of opportunistic infection. * Adequate baseline hematological and organ function as assessed by the following laboratory values within 28 days prior to study entry: Hemoglobin \>/=9 g/dL Granulocytes \>/=2,000/mm3 Lymphocytes \>/=1000/mm3 Platelets \>100,000/mm3 Serum Creatinine \</=1.5 X the ULN AST, ALT, GGT, CPK, LDH, Alk phos \</=2.5 X the ULN Serum Bilirubin \</=1.5 X ULN In addition to study entry, the above hematological and organ function lab values along with the ECOG PS must be met prior to starting IFNα treatment. * Subjects must have normal coagulation parameters as measured by PT/PTT,unless the subject is on an anticoagulation therapy.
Exclusion criteria
* Females of child-bearing potential (pre-menopausal) must have a negative serum beta-HCG pregnancy test at screening. * Subjects with acute infection: any acute viral, bacterial, or fungal infection which requires specific therapy. Acute therapy must have been completed more than 14 days prior to study treatment. * Hep B & C and HIV-infected patients, due to concerns in the ability to stimulate an effective immune response (determined by historical medical data). * Subjects with acute medical problems such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk. * Subjects with any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents). * Subjects with organ allografts. * Subjects must be free of known brain metastases by contrast-enhanced CT/MRI scans or have successfully-treated brain metastases and be asymptomatic for more than 1 month. * Patients requiring immunosuppressive therapy for comorbid conditions. * Concomitant Medication and Treatment: All allowed medications or treatments should be kept to a minimum and recorded. All questions regarding concomitant medications should be referred to the Investigator. * Long term concurrent medications and/or treatments Not Allowed: Corticosteroids, chemotherapy, cyclosporin A. Short term (approximately 1 week) use of topical, low-dose or inhaled steroids may be allowed at the discretion of the investigator. Injectables not allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 2 years | Types of adverse events associated with this Multiple Antigen-Engineered DC vaccine at the injection site and systemically. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunological response (antigen-specific T cell activation) | 2 years | Antigen-specific T cell activation will be monitored. |
Countries
United States
Outcome results
None listed