Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Active 21 to 75 Other Baylor IRB #006-025-01 0000, NCT00313235

Trial Description

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.

Further Study Information

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 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 2 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).

Trial Contact Information

Trial Lead Organizations/Sponsors

Baylor University Medical Center - Dallas

Joseph Wayne Fay

Principal Investigator

Anna Karolina Palucka, MD, PhD

Study Director

Susan Hicks		Ph: 214-820-7439
		Email: susanhi@baylorhealth.edu

U.S.A.
Texas
	Dallas
	Baylor University Medical Center - Dallas
		Baylor Information Services	Ph: 800-422-9567
		Doris Wood	Ph: 214-820-2610
			Email: dorisw@baylorhealth.edu
		Joseph Wayne Fay	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00313235
Information obtained from ClinicalTrials.gov on August 11, 2008