Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy and Autologous Lymphocyte Infusion With or Without Fludarabine in Treating Patients With Metastatic Melanoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Active 16 and over NCI MCC-13649 LAC-USC-10M-05-2, 6241, NCI-6241, LAC-USC-HS-05-00068, NCT00313508

Objectives

Primary

1. Assess the toxicity and immune responses in HLA-A*0201-positive patients with chemotherapy-naïve metastatic melanoma treated with either escalating doses of fludarabine or no fludarabine followed by autologous lymphocyte infusion and vaccination with dendritic cells matured ex vivo with a cytokine cocktail and pulsed with MART-1/gp100/tyrosinase/NY-ESO-1/MAGE-3 class I and II peptides.

Secondary

1. Compare clinical responses in patients receiving these regimens.

Entry Criteria

Disease Characteristics:

• Diagnosis of metastatic melanoma
  • The following subtypes are also eligible:
    • Unresectable stage III or IV uveal melanoma
    • Metastatic mucosal melanoma



• Measurable disease after attempted curative surgical therapy



• Tumor tissue must be available for immunohistochemical staining
  • Positive for ≥ 1 of the following peptides:
    • MART-1
    • Tyrosinase
    • NY-ESO-1
    • HMB-45



• HLA-A *0201 positive



• Positive for DR4 and/or DP4 by DNA SSOP analysis

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior chemotherapy
• Prior adjuvant interferon or isolated limb perfusion allowed
• More than 1 month since prior and no other concurrent therapy for melanoma, including radiotherapy, chemotherapy, or adjuvant therapy
• At least 1 month since prior surgery
• No concurrent steroid therapy
• No prior gp100 209-217 (210M), MART-1 26-35 (27L), gp100 280-288 (288V), tyrosinase 207-215, or NY-ESO-1 157-165 (165V) peptides

Patient Characteristics:

• ECOG performance status 0 or 1
• WBC ≥ 3,000/mm³
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 2.0 mg/dL
• ALT/AST < 3 times upper limit of normal
• Creatinine ≤ 2.0 mg/dL
• Seropositive for Epstein-Barr virus
• No major systemic infections
• No coagulation disorders
• No documented myocardial infarction in the past 6 months
• No other major medical illnesses of the cardiovascular or respiratory systems
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known positivity for hepatitis B surface antigen or hepatitis C antibody
• No known HIV positivity
• No prior uveitis or autoimmune inflammatory eye disease
• No other malignancy except for cervical carcinoma in situ or basal cell or squamous cell skin cancer unless patient was curatively treated > 5 years ago and has no detectable disease
• No history of any of the following:
  • Hypogammaglobulinemia
  • Lymphocytopenia
  • Impaired immune response
  • Tuberculosis or positive PPD unless patient received prior bacilli Calmette-Guérin vaccine (BCG)

Expected Enrollment

A total of 48 patients will be accrued for this study.

Outcomes

Overall survival
Progression-free survival
Time to progression

Immunological response in patients receiving MART-1/gp100/tyrosinase/NY-ESO-1 with fludarabine
Toxicity of MART-1/gp100/tyrosinase/NY-ESO-1 with fludarabine

Outline

This is a randomized, controlled, multicenter, dose-escalation study of fludarabine. Patients are randomized to 1 of 2 treatment arms.

All patients undergo two apheresis procedures, one to collect lymphocytes for the autologous lymphocyte infusion and one to collect dendritic cells (DC) for the production of the autologous vaccine. Autologous DC are pulsed with tumor antigen class I and II peptides derived from MART-1, gp100, tyrosinase, NY-ESO-1, and MAGE-3 and matured with a cytokine cocktail comprising tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and prostaglandin E2.

• Arm I: Patients receive fludarabine IV over 30 minutes on days -7 to -3 (beginning 3 days after the second apheresis procedure). Patients receive autologous lymphocyte infusion IV over 1 hour on day 0 followed by vaccination with autologous peptide-pulsed DC intranodally over 24 hours on days 1, 8, 22, and 36. Patients who have stable disease or who achieve a response to treatment may receive re-treatment with fludarabine, autologous lymphocyte infusion, and autologous peptide-pulsed DC vaccine (as above) approximately 4 weeks to 6 months after the last DC vaccine.

  Cohorts of 3-12 patients receive escalating doses of fludarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or 3 of 12 patients experience dose-limiting toxicity.




• Arm II: Patients receive autologous lymphocyte infusion and vaccination with autologous peptide-pulsed DC as in arm I. Patients who have stable disease or who achieve a response to treatment may receive re-treatment with autologous lymphocyte infusion and autologous peptide-pulsed DC vaccine (as in arm I) approximately 4 weeks to 6 months after the last DC vaccine.

After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Jeffrey Weber, MD, PhD, Protocol chair		Ph: 813-745-4261; 888-663-3488

U.S.A.
Florida
	Tampa
	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
		Clinical Trials Office - H. Lee Moffitt Cancer Center and Reseach Institute	Ph:  800-456-7121
			Email: canceranswers@moffitt.org

Registry Information
Official Title		A Dose Ranging Trial of MART-1/gp100/Tyrosinase/NY-ESO-1 Peptide-Pulsed Dendritic Cells Matured Using Cytokines with Autologous Lymphocyte Infusion With or Without Escalating Doses of Fludarabine for Patients With Chemotherapy-naive Metastatic Melanoma
Trial Start Date		2006-02-01
Trial Completion Date		2009-03-02 (estimated)
Registered in ClinicalTrials.gov		NCT00313508
Date Submitted to PDQ		2005-12-22
Information Last Verified		2008-04-10
NCI Grant/Contract Number		CA14089, CA105139, CA76292