Multiple Antigen-Engineered DC Vaccine for Melanoma

NCT01622933 | Completed Phase 1 DMC

• 2 other identifiers: 09-0211P50CA121973-01A1
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Keywords

melanoma; recurrent; metastatic

Outcome Measures

Primary Outcomes (1)

• Safety

  Types of adverse events associated with this Multiple Antigen-Engineered DC vaccine at the injection site and systemically.

  2 years

Secondary Outcomes (1)

• Immunological response (antigen-specific T cell activation)

  2 years

Study Arms (2)

Vaccine + IFN

EXPERIMENTAL

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.

Biological: DC Vaccine + IFN

Vaccine only

EXPERIMENTAL

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.

Biological: AdVTMM2/DC Vaccination

Interventions

DC Vaccine + IFN BIOLOGICAL

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.

Also known as: Interferon Alfa - 2b, Intron A, IFN-alpha 2b, NSC #377523, IFNα, AdVTMM2/DC Vaccination

Vaccine + IFN

AdVTMM2/DC Vaccination BIOLOGICAL

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.

Vaccine only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lisa H. Butterfield, Ph.D.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Butterfield LH, Vujanovic L, Santos PM, Maurer DM, Gambotto A, Lohr J, Li C, Waldman J, Chandran U, Lin Y, Lin H, Tawbi HA, Tarhini AA, Kirkwood JM. Multiple antigen-engineered DC vaccines with or without IFNalpha to promote antitumor immunity in melanoma. J Immunother Cancer. 2019 Apr 24;7(1):113. doi: 10.1186/s40425-019-0552-x.

  PMID: 31014399 DERIVED

MeSH Terms

Conditions

Melanoma; Recurrence; Neoplasm Metastasis

Interventions

Introns

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes

Study Officials

• John M Kirkwood, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 19, 2012
• Study Start: June 1, 2012
• Primary Completion: May 1, 2016
• Study Completion: August 1, 2017
• Last Updated: August 31, 2017

Record last verified: 2016-05

Locations

US (1)