Combined Modality Treatment for Patients With Stage IV Melanoma - Full Text View

Sponsors and Collaborators:	Baylor Research Institute Baylor University
Information provided by:	Baylor Research Institute
ClinicalTrials.gov Identifier:	NCT00313235

Purpose

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.

Condition	Intervention	Phase
Stage IV Metastatic Melanoma	Biological: Dendritic cell vaccination	Phase I Phase II

MedlinePlus related topics: Melanoma

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Combined Modality Treatment for Patients With Stage IV Melanoma: Cyclophosphamide and a Dendritic Cell Vaccine Loaded With Killed Allogeneic Melanoma Cells

Further study details as provided by Baylor Research Institute:

Primary Outcome Measures:

Safety and tolerability of the combination of DC vaccination and CPA therapy in human subjects [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
Feasibility of this combination therapy [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
Objective clinical responses [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
Feasibility of shipping vaccines [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Immunogenicity of DC vaccinations in subjects pretreated with CPA [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
Effect of CPA at this dose and schedule on the frequency of regulatory/suppressor T cells [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	33
Study Start Date:	March 2006
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Intervention Details:

Autologous dendritic cells derived from PBMC, cultured with cytokines, pulsed ex vivo with irradiated allogeneic (Colo 829) melanoma cells

Detailed Description:

A novel dendritic cell vaccine has been 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. A 15% objective response rate will be accepted in patients who have failed previous therapy with dacarbazine (DTIC) and/or temozolomide, alone or in combination with other cytotoxic agents and with or without IL-2.

Patients will receive cyclophosphamide 300 mg/m2, administered 24 hours prior to DC vaccinations # 1, 3, 5, 6 and 7. Each subject will initially be given 7 initial injections in a fixed dose amount with each individual dose being administered at weeks 0, 2, 4, 6, 10, 14 and 18. 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.

Eligibility

Ages Eligible for Study:	21 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.
Patients with or without a history of CNS melanoma lesions. 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 melanoma.
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 trial.
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 thyroiditis.
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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313235

Contacts

Contact: Susan Hicks

214-820-7439

susanhi@baylorhealth.edu

Locations

United States, Texas
Baylor University Medical Center	Recruiting
Dallas, Texas, United States, 75246
Contact: Baylor Information Services 800-422-9567
Contact: Doris Wood 214-820-2610 dorisw@baylorhealth.edu
Principal Investigator: Joseph W. Fay, M.D.

Sponsors and Collaborators

Baylor Research Institute

Baylor University

Investigators

Principal Investigator:	Joseph W. Fay, MD	Baylor University
Study Director:	Anna Karolina Palucka, MD, PhD	Baylor University

More Information

Responsible Party:	Baylor Institute for Immunology Research ( Joseph Fay, M.D. )
Study ID Numbers:	Baylor IRB #006-025-01, 0000
Study First Received:	April 10, 2006
Last Updated:	January 9, 2009
ClinicalTrials.gov Identifier:	NCT00313235
Health Authority:	United States: Food and Drug Administration

Keywords provided by Baylor Research Institute:

Dendritic
Vaccine
Melanoma
Cyclophosphamide (CPA)

Study placed in the following topic categories:

Neuroectodermal Tumors
Nevus, Pigmented
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma

Cyclophosphamide
Nevus
Neuroendocrine Tumors
Melanoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Therapeutic Uses
Myeloablative Agonists
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009