Vaccine Therapy and Autologous Lymphocyte Infusion With or Without Fludarabine in Treating Patients With Metastatic Melanoma - Full Text View

Sponsors and Collaborators:	H. Lee Moffitt Cancer Center and Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00313508

Purpose

RATIONALE: Vaccines made from a person's dendritic cells that have been treated in the laboratory may help the body build an effective immune response to kill tumor cells. Giving an infusion of autologous lymphocytes and then infusing the vaccine directly into a lymph node may cause a stronger immune response and kill more tumor cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vaccine therapy and autologous lymphocyte infusion together with fludarabine may kill more tumor cells.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of fludarabine followed by autologous lymphocyte infusion and vaccine therapy and to see how well it works in treating patients with metastatic melanoma.

Condition	Intervention	Phase
Intraocular Melanoma Melanoma (Skin)	Biological: dendritic cell vaccine therapy Biological: therapeutic autologous lymphocytes Drug: fludarabine phosphate	Phase I Phase II

Genetics Home Reference related topics: retinoblastoma

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Fludarabine Fludarabine monophosphate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]

Secondary Outcome Measures:

Immunological response in patients receiving MART-1/gp100/tyrosinase/NY-ESO-1 with fludarabine [ Designated as safety issue: No ]
Toxicity of MART-1/gp100/tyrosinase/NY-ESO-1 with fludarabine [ Designated as safety issue: Yes ]

Estimated Enrollment:	48
Study Start Date:	February 2006
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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.	Biological: dendritic cell vaccine therapy Given intranodally Biological: therapeutic autologous lymphocytes Given IV Drug: fludarabine phosphate Given IV
Arm II: Experimental 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.	Biological: dendritic cell vaccine therapy Given intranodally Biological: therapeutic autologous lymphocytes Given IV

Arms

Assigned Interventions

Arm I: Experimental

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.

Biological: dendritic cell vaccine therapy

Given intranodally

Biological: therapeutic autologous lymphocytes

Given IV

Drug: fludarabine phosphate

Given IV

Arm II: Experimental

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.

Biological: dendritic cell vaccine therapy

Given intranodally

Biological: therapeutic autologous lymphocytes

Given IV

Detailed Description:

OBJECTIVES:

Primary

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

Compare clinical responses in patients receiving these regimens.

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.

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

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

PATIENT CHARACTERISTICS:

ECOG performance status 0 or 1
WBC ≥ 3,000/mm^3
Hemoglobin ≥ 9.0 g/dL
Platelet count ≥ 100,000/mm^3
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)

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313508

Locations

United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Recruiting
Tampa, Florida, United States, 33612-9497
Contact: Clinical Trials Office - H. Lee Moffitt Cancer Center and Rese 800-456-7121 canceranswers@moffitt.org

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Jeffrey S. Weber, MD, PhD

H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida ( Jeffrey S. Weber )
Study ID Numbers:	CDR0000465200, MCC-13649, LAC-USC-10M-05-2, NCI-6241, LAC-USC-HS-05-00068
Study First Received:	April 11, 2006
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00313508 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IV melanoma
recurrent melanoma
ciliary body and choroid melanoma, medium/large size
recurrent intraocular melanoma

metastatic intraocular melanoma
extraocular extension melanoma
iris melanoma

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Eye Neoplasms
Uveal Melanoma
Eye Diseases
Melanoma of the Choroid
Fludarabine monophosphate
Immunosuppressive Agents
Recurrence

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Intraocular Melanoma
Neuroepithelioma
Fludarabine
Nevus

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Eye Neoplasms
Antineoplastic Agents
Eye Diseases
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Fludarabine monophosphate

Immunosuppressive Agents
Pharmacologic Actions
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Fludarabine

ClinicalTrials.gov processed this record on May 07, 2009