Combined Modality Treatment for Patients With Stage IV Melanoma: Cyclophosphamide and a Dendritic Cell Vaccine Loaded With Killed Allogeneic Melanoma Cells
A novel dendritic cell vaccine is being developed at the Baylor Institute for Immunology
Research. Pre-clinical studies have found that this dendritic cell vaccine is more
efficient in inducing a tumor specific immunity than other dendritic cell vaccines. Further
studies in BIIR have been done with dendritic cells that were loaded with killed melanoma
cells from a melanoma cell line treated with heat before loading. Both studies have shown
that DCs manufactured in this novel way were more efficient in priming the melanoma specific
CD8+ cells. Our previous studies indicate that a portion of patients with stage IV melanoma
cannot mount an immune response to tumor antigens presented on dendritic cells. Also,
regulatory/suppressor T cells can be identified in the blood of these patients, which may
account for the lack of induction of T cell immunity to dendritic cell vaccines.
Cyclophosphamide treatments have improved antitumor immunity in humans with melanoma and a
clear relationship between cyclophosphamide dosage and suppressor cell activity has been
documented. Therefore, this trial will test a combined modality treatment, using dendritic
cell based vaccines in patients who have been treated with cyclophosphamide.
This clinical trial will evaluate the cyclophosphamide/dendritic cell vaccine in patients
with Stage IV melanoma. The trial will accrue a total of 33 subjects. The primary goal of
this trial will be to test the safety/tolerability/feasibility of the combined modality and
the rate of objective clinical response.However if feasibility data in the first 10 subjects
demonstrate the need to adjust the dose of CPA, the new dose will be tested in the next 10
subjects thereby extending the accrual to 43 subjects. A 15% objective response rate will be
accepted in patients with stage IV Melanoma.
Patients will receive cyclophosphamide 300 mg/m2, administered 24 hours prior to DC
vaccinations # 1, 3, 5, 6 and 7. Each subject will initially receive 7 doses of vaccination
with each individual dose being administered at weeks 0, 2, 4, 6, 10, 14 and 18. A clinical
evaluation of the patients will be done at weeks 10 & 20. Patients with progressive disease
will be taken off of the study. Patients with SD, PR or CD (according to RECIST criteria)
may receive 4 more vaccinations. Scans and re-staging tests will be performed at scheduled
intervals throughout the study.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability of the combination of DC vaccination and CPA therapy in human subjects
2 Years
Yes
Joseph W. Fay, MD
Principal Investigator
Baylor Health Care System
United States: Food and Drug Administration
Baylor IRB #006-025-01
NCT00313235
March 2006
June 2012
Name | Location |
---|---|
Baylor University Medical Center | Dallas, Texas 75246 |