Combined Modality Treatment for Patients With Stage IV Melanoma
Condition: Malignant Melanoma Stage IV
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to test a combined treatment using cyclophosphamide and a novel
      dendritic cell vaccine in patients with Stage IV melanoma.
    

Detailed description: 
      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.
    

Intervention name(s): DC Vaccine and Cyclophosphamide
Intervention type(s): Biological
Intervention description(s): Autologous dendritic cells (DC) are derived from PBMC, cultured with cytokines, pulsed ex vivo with irradiated allogeneic (Colo 829) melanoma cells. About 15 x 10^6 dendritic cells will be injected subcutaneously, in 3 separate sites (3.3 ml/site).
Patients will receive a total of 7 doses of the vaccination. Each individual dose will be administered at weeks: 0, 2, 4, 6, 11, 14, and 18. Patients with SD, PR according to RECIST criteria may receive 4 more vaccines at 36, 48, 60 and 72 weeks. Patients with CR will receive 4 additional vaccines at 36, 48, 72, and 96 weeks.
CPA will be administered 300mg/m2, intravenously over a 2-hour infusion 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7. Frequency of CPA administration might be increased based on their T cell measure.
Other intervention name(s): Cyclophosphamide - CPA; Dendritic Cell Vaccine - DC Vaccine
Intervention MeSH terms: Cyclophosphamide; Vaccines
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dendritic Vaccine; Melanoma; Cyclophosphamide (CPA)