Multiple Antigen-Engineered DC Vaccine for Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Lisa H. Butterfield, Ph.D., University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01622933
First received: June 14, 2012
Last updated: June 5, 2014
Last verified: June 2014

June 14, 2012
June 5, 2014
June 2012
June 2015   (final data collection date for primary outcome measure)
Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Types of adverse events associated with this Multiple Antigen-Engineered DC vaccine at the injection site and systemically.
Same as current
Complete list of historical versions of study NCT01622933 on ClinicalTrials.gov Archive Site
Immunological response (antigen-specific T cell activation) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Antigen-specific T cell activation will be monitored.
Same as current
Not Provided
Not Provided
 
Multiple Antigen-Engineered DC Vaccine for Melanoma
A Phase I Trial Testing Multiple Antigen-Engineered DC Followed by IFNa2b Boost for Immunization of HLA-Unrestricted Melanoma Patients

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 30 days after the 3rd vaccine.

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 30 days after the 3rd vaccine.

The end-points of this study are local and systemic toxicity, immunological response, generation of determinant spreading and anti-tumor immunity, and clinical response.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
  • Biological: DC Vaccine + IFN
    Vaccine: The dose target is 1x10e7 AdVTMM2/DC per intradermal injection. 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.
    Other Names:
    • Interferon Alfa - 2b
    • Intron A
    • IFN-alpha 2b
    • NSC #377523
    • IFNα
    • AdVTMM2/DC Vaccination
  • Biological: AdVTMM2/DC Vaccination
    Vaccine: The dose target is 1x10e7 AdVTMM2/DC per intradermal injection.
    Other Name: AdVTMM2/DC Vaccination
  • Experimental: Vaccine + IFN

    Subjects will receive the investigational vaccine, intradermally, every other week for a total of 3 vaccines. Approximately 30 days after the last vaccine subjects will receive IFN intravenously 5 days a week for 4 weeks.

    Leukapheresis will be required to be performed for each subject to be able to produce the investigational vaccine and for research testing. Leukapheresis and biopsies will be performed before the first vaccine, after the 3rd vaccine, and after the IFN treatment.

    Intervention: Biological: DC Vaccine + IFN
  • Experimental: Vaccine only

    Subjects will receive the investigational vaccine, intradermally, every other week for a total of 3 vaccines.

    Leukapheresis will be required to be performed for each subject to be able to produce the investigational vaccine and for research testing. Leukapheresis and biopsies will be performed before the first vaccine, after the 3rd vaccine, and again approximately 2 months after the last vaccine.

    Intervention: Biological: AdVTMM2/DC Vaccination
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
June 2015
June 2015   (final data collection date for primary outcome measure)

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.

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.
  • Previous clinical evidence of an autoimmune disease.
  • 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.
Both
18 Years and older
No
Contact: John M Kirkwood, MD (412) 623-7707 kirkwoodjm@upmc.edu
Contact: Mollie Maguire, RN, BSN (412) 623-4004 maguiremd@upmc.edu
United States
 
NCT01622933
09-021, 1P50CA121973-01A1
Yes
Lisa H. Butterfield, Ph.D., University of Pittsburgh
Lisa H. Butterfield, Ph.D.
National Cancer Institute (NCI)
Principal Investigator: John M Kirkwood, MD University of Pittsburgh
University of Pittsburgh
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP