Vaccine Therapy With or Without Interleukin-2 After Chemotherapy and an Autologous White Blood Cell Infusion in Treating Patients With Metastatic Melanoma - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00303836

Purpose

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy with interleukin-2, chemotherapy, and an autologous white blood cell infusion may be a more effective treatment for metastatic melanoma.

PURPOSE: This randomized phase II trial is studying how well giving vaccine therapy with or without interleukin-2 after chemotherapy and an autologous white blood cell infusion works in treating patients with metastatic melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Drug: MART-1 antigen Drug: aldesleukin Drug: cyclophosphamide Drug: filgrastim Drug: fludarabine phosphate Drug: gp100 antigen Drug: incomplete Freund's adjuvant Drug: therapeutic autologous lymphocytes Procedure: in vitro-treated peripheral blood stem cell transplantation	Phase II

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Cyclophosphamide Filgrastim Fludarabine Fludarabine monophosphate Aldesleukin Interleukin-2 Freund's adjuvant Montanide ISA 51

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	A Phase II Study Using A Peptide Vaccine With or Without Aldesleukin Following a Lymphodepleting Chemotherapy and Reinfusion of Autologous Lymphocytes Depleted of T Regulatory Lymphocytes in Metastatic Melanoma

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

Primary Outcome Measures:

Tumor regression [ Designated as safety issue: No ]

Secondary Outcome Measures:

Generation of antitumor lymphocytes and rate of repopulation of CD25+ T-regulatory cells [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	58
Study Start Date:	December 2005

Detailed Description:

OBJECTIVES:

Primary

Determine the ability of gp100 and MART-1 peptide vaccines with or without a high-dose interleukin-2 (IL-2), when administered after a nonmyeloablative, lymphodepleting preparative regimen and reinfusion of autologous CD25+ T-regulatory-depleted lymphocytes, to mediate tumor regression in patients with metastatic melanoma.

Secondary

Determine the generation of antitumor lymphocytes and the rate of repopulation of CD25+ T-regulatory cells in patients treated with this regimen.
Determine the toxicity of this treatment regimen.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo apheresis and in-vitro depletion of T-regulatory cells. Patients then receive a nonmyeloablative, lymphocyte-depleting preparative regimen comprising cyclophosphamide IV over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on days -6 to -2 followed by autologous T-regulatory-depleted lymphocytes IV over 20-30 minutes on day 0. Patients receive vaccination with gp100:209-217 (210M) and MART-1:27-35 peptides emulsified in Montanide ISA-51 subcutaneously (SC) on days 0-3, 20-23, 41-44, and 62-65. Patients also receive filgrastim (G-CSF) SC beginning on day 1 and continuing until blood counts recover.
Arm II: Patients receive treatment as in arm I. Patients also receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0-4, beginning after the lymphocyte infusion. IL-2 treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 1-3 months.

PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of metastatic melanoma
- No tumor reactive cells available for cell transfer therapy
Measurable disease
Previously treated with interleukin-2 (IL-2) and meets 1 of the following criteria:
- No response (progressive disease)
- Recurrent disease
HLA*0201 positive

PATIENT CHARACTERISTICS:

ECOG performance status 0 or 1
Absolute neutrophil count > 1,000/mm^3
Platelet count > 100,000/mm^3
Hemoglobin > 8.0 g/dL
ALT and AST < 3 times upper limit of normal
Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL if Gilbert's disease is present)
Creatinine ≤ 2.0 mg/dL
Life expectancy ≥ 3 months
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for up to 4 months after receiving the preparative regimen
No active systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular, respiratory, or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, or obstructive or restrictive pulmonary disease
No autoimmune disease (e.g., autoimmune colitis or Crohn's disease) or primary immunodeficiency disease
No HIV positivity
No hepatitis B or C virus positivity
No Epstein-Barr virus negativity
Eligible to receive high-dose IL-2, as evidenced by the following:
- Patients ≥ 50 years of age must have a normal cardiac stress test (e.g., stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) AND LVEF ≥ 45%
- Patients with a history of EKG abnormalities, symptoms of cardiac ischemia, or arrhythmias must have a normal cardiac stress test AND LVEF ≥ 45%
- Patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test, as evidenced by FEV_1 ≥ 60% of predicted

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 4 weeks since prior systemic therapy
At least 6 weeks since prior nitrosourea therapy
No concurrent systemic steroid therapy
Recovered immune competence after prior chemotherapy or radiotherapy
No prior gp100:209-217 or MART-1:27-35 peptide vaccine

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303836

Locations

United States, Maryland
NCI - Surgery Branch
Bethesda, Maryland, United States, 20892-1201
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Steven A. Rosenberg, MD, PhD

NCI - Surgery Branch

More Information

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

Study ID Numbers:	CDR0000459683, NCI-06-C-0028, NCI-7547, NCI-P6574
Study First Received:	March 15, 2006
Last Updated:	December 13, 2008
ClinicalTrials.gov Identifier:	NCT00303836
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage IV melanoma
recurrent melanoma

Study placed in the following topic categories:

Cyclophosphamide
Fludarabine monophosphate
Recurrence
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Aldesleukin

Interleukin-2
Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Neuroepithelioma
Freund's Adjuvant
Nevus
Fludarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Anti-HIV Agents
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Adjuvants, Immunologic

Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Anti-Retroviral Agents
Therapeutic Uses
Myeloablative Agonists
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009