Vaccination With Autologous, Lethally Irradiated Melanoma Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete Granulocyte-Macrophage Stimulating Factor (GMSF)

A Phase IB Study of Vaccination With Autologous, Lethally Irradiated Melanoma Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete Human Granulocyte-Macrophage Stimulating Factor

The purpose of this study is to see if the proposed therapy will delay or stop the progression of the participants skin cancer. This study is being done because there are currently no treatments which have been shown convincing to treat disease which has progressed. This research study is designed to evaluate the immunologic effects and clinical side effects of giving vaccines to patients that are made from their own skin cancer cells.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: Autologous, lethally irradiated melanoma cells

Detailed Description

• The vaccines created from the participants melanoma cells are scheduled to be given to the participants on days 1, 8, 15, 29 and every two weeks after until the supply of vaccine has run out. The amount of vaccine is dependent on the total amount of cells yielded when the tumor is processed and treated. It is hoped that participants will receive at least six vaccines.
• The vaccines will be administered in two injections that will be placed underneath the participants skin. The two injections will be given at the same place on the body.
• If tumor sample yields enough cells, participants will also receive an injection of non-transduced irradiated melanoma cells. The purpose of this is to measure the amount of reaction of the participants immune system occuring created by the vaccine.
• If either the vaccine site or DTH placement site has shown a reaction, a punch-biopsy will be taken. This will consist of a small piece of skin tissue removed under local anesthesia.
• With vaccine #5, participants will receive a second DTH injection. Two days after the vaccine and DTH injection, punch biopsies will be taken of both sites.
• At week 10 of treatment (or earlier if necessary), participants will undergo a chest, abdomen and pelvic CT scan. The physician may also have participants undergo a brain MRI if indicated at this time.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Stage III patients must have: A) Histologically documented melanoma B) Lymphadenopathy of at least 2cm in greatest diameter by physical exam or CT scan in a region draining a known or suspected primary melanoma or in transit metastatic disease of at least 2cm in greatest diameter by physical exam or CT in a region draining a known primary melanoma C) refused, not eligible, or failed adjuvant therapy with high dose a-interferon D) must be able to have all measurable disease removed at time of tumor harvest
• Stage IV patients must have histologically documented metastatic melanoma
• ECOG Performance Status 0 or 1
• Estimated life expectancy of 6 months or greater
• 18 years of age or older
• Signed Informed Consent
• Greater than 4 weeks from any chemotherapy, radiotherapy, immunotherapy, or systemic glucocorticoid therapy
• Greater than 6 months since bone marrow or peripheral blood stem cell transplant

Exclusion Criteria:

• Uncontrolled active infection
• Pregnancy or nursing mothers
• Evidence of infection with Human Immunodeficiency Virus, Hepatitis B or C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melanoma Vaccine; GM-CSF Vaccine	Biological: Autologous, lethally irradiated melanoma cells; Engineered to secrete human granulocyte-macrophage stimulating factor. Given on days 1, 8, 15, 29 and every two weeks after until the supply of vaccine has run out

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the doses of lethally irradiated, autologous melanoma cells engineered by adenoviral mediated gene transfer to secrete CM-CSF that can be manufactured in stage III melanoma patients.	7 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and biologic activity of vaccination with lethally irradiated, autologous melanoma cells engineered by adenoviral mediated gene transfer to secrete GM-CSF	7 years
To determine the two-year survival of stage IV melanoma patients vaccinated with lethally irradiated, autologous melanoma cells engineered by adenoviral mediated gene transfer to secrete GM-CSF	7 years
To determine more fully the safety and biologic activity of vaccination with lethally irradiated, autologous melanoma cells engineered by adenoviral mediated gene transfer to secrete GM-CSF in stage IV melanoma patients	7 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Massachusetts General Hospital; Brigham and Women's Hospital
• Investigators: Principal Investigator: F. Stephen Hodi, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2003
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): February 25, 2020

Study Registration Dates

• First Submitted: December 16, 2008
• First Submitted That Met QC Criteria: December 16, 2008
• First Posted (Estimated): December 17, 2008

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: vaccination; autologous; GM-CSF; irradiated
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: 03-218