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Combined Modality Treatment for Patients With Stage IV Melanoma: Cyclophosphamide and a Dendritic Cell Vaccine Loaded With Killed Allogeneic Melanoma Cells

Phase 1/Phase 2
21 Years
75 Years
Not Enrolling
Malignant Melanoma Stage IV

Thank you

Trial Information

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.

Inclusion Criteria:

- Stage M1a, M1b, M1c biopsy proven metastatic melanoma.

- Ages 21-75.

- Karnofsky performance status greater than/equal to 80%.

- Measurable metastatic lesions by physical exam or scans.

- Acceptable CBC and blood chemistry results.

- Adequate hepatic and renal function.

- No active CNS metastatic disease. If CNS history is present, lesions must have been
resected by surgery and/or gamma knife irradiation at least 3 months prior to study
entry. The total number of CNS lesions at diagnosis should not exceed 3.

- Written informed consent.

Exclusion Criteria:

- Patients that have received more than 8 cycles of chemotherapy for metastatic

- Patients who have received chemotherapy less than 4 weeks before beginning the trial.

- Patients who have received IFN alpha-2b or GM-CSF less than 4 weeks before beginning
the trial.

- Patients who have received high-dose IL-2 less than 4 weeks before beginning the

- Patients diagnosed with more than 3 CNS metastatic melanoma lesions.

- More than 5 hepatic lesions or any hepatic lesion larger than 5 cm.

- Baseline serum LDH greater than 1.1 times the upper limit of normal.

- Patients who are HIV positive.

- Patients who are pregnant.

- Patients who have receive corticosteroids or other agents less than 4 weeks before
beginning the trial.

- Patients with asthma, angina pectoris or congestive heart failure.

- Patients with autoimmune disease such as lupus erythematosus, rheumatoid arthritis or

- Patients with active infections including viral hepatitis.

- Patients with a history of any other neoplastic disease less than 5 years ago
(carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin,
however, can be admitted to the study).

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability of the combination of DC vaccination and CPA therapy in human subjects

Outcome Time Frame:

2 Years

Safety Issue:


Principal Investigator

Joseph W. Fay, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor Health Care System


United States: Food and Drug Administration

Study ID:

Baylor IRB #006-025-01



Start Date:

March 2006

Completion Date:

June 2012

Related Keywords:

  • Malignant Melanoma Stage IV
  • Dendritic Vaccine
  • Melanoma
  • Cyclophosphamide (CPA)
  • Melanoma



Baylor University Medical CenterDallas, Texas  75246