Comparison Study of Dendritic Cell Vaccine With and Without Cyclophosphamide to Treat Stage IV Melanoma Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the combination of chemotherapy (Cyclophosphamide) and CD34-DC vaccines results in the improved rate of clinical responses for stage IV melanoma patients.

Detailed Description
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Vaccination of patients with metastatic melanoma using ex vivo generated dendritic cells (DCs) loaded with tumor-associated antigen(s) have been shown to induce tumor-specific immunity against melanoma antigens measured by in vitro assays and, in some cases, tumor regression. At the present time, the numbers of recorded patients with metastatic melanoma who have been treated with DC vaccinations are too small to predict with certainty the future of overall therapeutic value of DC vaccinations in the management of patients with metastatic melanoma. The purpose of this study is to gather data on feasibility and efficacy of novel combination therapy of CPA and a DC vaccine outlined in this protocol to treat metastatic melanoma.

Official Title
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Melanoma Peptide-Loaded Dendritic Cell Vaccine in HLA-A*0201 Patients With Stage IV Melanoma: A Phase II Randomized Trial to Compare Vaccination With and Without Cyclophosphamide Treatment.

Conditions
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Malignant Melanoma Stage IV

Intervention / Treatment
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* Biological: DC Vaccine & Cyclophosphamide
* Biological: DC Vaccine & Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven metastatic melanoma, Stages M1a, M1b, M1c HLA-A*0201 phenotype Age: 21-75 years ECOG performance status 0-1 Measurable metastatic melanoma lesions by physical examination or radiographs or scans. Adequate marrow function: White count ≥ 4,000/microliter: Subjects who have recently completed chemotherapy will be allowed study entry with White count ≥ 3,500/microliter Hemoglobin ≥ 10.0 gm: Subjects who have recently completed chemotherapy will be allowed study entry with Hemoglobin ≥ 9.0 gm. Platelets ≥ 100,000/microliter Adequate hepatic function: Bilirubin ≤ 1.5/mg/dL Alkaline phosphatase ≤ 5 times the upper limit of normal SGOT ≤ 5 times the upper limit of normal SGPT ≤ 5 times the upper limit of normal Adequate renal function: Serum creatinine ≤ 1.5/mg/dL No active CNS metastatic disease at screening. Patients with a history of CNS melanoma lesions must have had lesions 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 have exceeded 3. Written informed consent Exclusion Criteria: Patients who have received > 8 cycles of cytotoxic chemotherapy or metastatic melanoma Patients who have received any chemotherapy < 4 weeks before the beginning of the trial Patients who have received interferon alpha (IFNα-2b) or sargramostim (GM-CSF) < 4 weeks before the beginning of the trial Patients who have received high-dose interleukin-2 (IL-2) < 4 weeks before the beginning of the trial Patients that have been diagnosed with more than 3 CNS melanoma lesions. Patients that have been diagnosed with more than 5 hepatic metastases or any hepatic metastasis > 5 cm. Baseline serum LDH > 1.1 times the upper limit of normal Patients who are HIV+ (HIV patients are often profoundly immunodeficient because of the viral infection and this additional parameter will interfere with the evaluation of DC induced immune responses in melanoma patients. Furthermore, the safety of collecting DCs, loading them with antigen and re-infusing these cells to HIV+ patients has not yet been determined.) Pregnancy (Pregnancy is associated with considerable immunosuppression 70 and this additional parameter will interfere with the evaluation of DC induced immune responses in melanoma patients. In addition, the safety and tolerability of cell body-loaded DC given subcutaneously is entirely unknown.) Patients who have received corticosteroids or other immunosuppressive agents < 4 weeks before beginning the trial Patients with active asthma and/or on treatment for asthma Patients with angina pectoris Patients with congestive heart failure Patients with a history of autoimmune disease including lupus erythematosus, rheumatoid arthritis or thyroiditis Patients with active infections including viral hepatitis Patients with a history of neoplastic disease other than melanoma < 5 years prior to entry on the trial except for patients with carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin. Patients who have any of these two types of cancer and melanoma can be included.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DC Vaccine & Cyclophosphamide<br>Patients will receive a fixed dose of about ≥15x106 viable dendritic cells per injection. Patients will receive a total of 8 doses of the vaccination with each individual dose being administered at weeks: 0, 2, 4, 6, 10, 14, 18 and 22. Responses will be evaluated and patients with SD, PR or CR may receive 4 more vaccine at 36, 48, 72 and 96 weeks, if there is vaccine available. The vaccine will be injected subcutaneously, in 3 separate injection sites (3.3.ml per site) in the upper and lower extremities. Patients will receive either CPA 300mg/m2 for injections administered intravenously over a 2-hour infusion in the outpatient clinic 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7. | Biological: DC Vaccine & Cyclophosphamide<br>* Patients will receive a fixed dose of about ≥15x106 viable dendritic cells per injection. Patients will receive a total of 8 doses of the vaccination with each individual dose being administered at weeks: 0, 2, 4, 6, 10, 14, 18 and 22. Responses will be evaluated and patients with SD, PR or CR may receive 4 more vaccine at 36, 48, 72 and 96 weeks, if there is vaccine available. The vaccine will be injected subcutaneously, in 3 separate injection sites (3.3.ml per site) in the upper and lower extremities. Patients will receive either CPA 300mg/m2 for injections administered intravenously over a 2-hour infusion in the outpatient clinic 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7.<br>* Other names: DC Vaccine ( Dendritic cell vaccine);|
| Placebo Comparator: DC Vaccine & Placebo<br>Patients will receive a fixed dose of about ≥15x106 viable dendritic cells per injection. Patients will receive a total of 8 doses of the vaccination with each individual dose being administered at weeks: 0, 2, 4, 6, 10, 14, 18 and 22. Responses will be evaluated and patients with SD, PR or CR may receive 4 more vaccine at 36, 48, 72 and 96 weeks, if there is vaccine available. The vaccine will be injected subcutaneously, in 3 separate injection sites (3.3.ml per site) in the upper and lower extremities. Patients will receive saline for injections administered intravenously over a 2-hour infusion in the outpatient clinic 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7. | Biological: DC Vaccine & Placebo<br>* Patients will receive a fixed dose of about ≥15x106 viable dendritic cells per injection. Patients will receive a total of 8 doses of the vaccination with each individual dose being administered at weeks: 0, 2, 4, 6, 10, 14, 18 and 22. Responses will be evaluated and patients with SD, PR or CR may receive 4 more vaccine at 36, 48, 72 and 96 weeks, if there is vaccine available. The vaccine will be injected subcutaneously, in 3 separate injection sites (3.3.ml per site) in the upper and lower extremities. Patients will receive saline for injections administered intravenously over a 2-hour infusion in the outpatient clinic 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7.<br>* Other names: DC Vaccine - Dendritic Cell Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction of melanoma-specific CD8+T Cell Immunity. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of objective clinical responses. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Dendritic Cell, Vaccine, Immunotherapy, Cyclophosphamide