Chemotherapy Consisting of Fludarabine and Cyclophosphamide Followed By White Blood Cell Infusion, Vaccine Therapy, and Aldesleukin in Treating Patients With Recurrent or Refractory Metastatic Melanoma - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00084500

Purpose

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Treated white blood cells, vaccines, and aldesleukin may make the body build an immune response to kill tumor cells.

PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with white blood cell infusion, vaccine therapy, and aldesleukin works in treating patients with recurrent or refractory metastatic melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Drug: aldesleukin Drug: cyclophosphamide Drug: filgrastim Drug: fludarabine phosphate Drug: fowlpox virus vaccine vector Drug: gp100 antigen Drug: therapeutic autologous lymphocytes Drug: therapeutic tumor infiltrating lymphocytes	Phase II

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Cyclophosphamide Filgrastim Fludarabine Fludarabine monophosphate Aldesleukin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study in Metastatic Melanoma Using Lymphocytes Reactive With the GP100 Antigen With Immunization Using a Recombinant RF-GP100P209 Virus Encoding a GP100 Peptide Following a Nonmyeloblative Lymphocyte Depleting Regimen

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

Primary Outcome Measures:

Complete clinical tumor response [ Designated as safety issue: No ]

Secondary Outcome Measures:

Survival [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]

Estimated Enrollment:	68
Study Start Date:	March 2004
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine complete clinical tumor regression in patients with recurrent or refractory metastatic melanoma treated with lymphocyte-depleting nonmyeloablative preparative chemotherapy comprising fludarabine and cyclophosphamide followed by autologous lymphocyte infusion, recombinant fowlpox virus encoding gp100 peptide, and aldesleukin.

Secondary

Determine the survival of patients treated with this regimen.
Determine the safety of this regimen in these patients.

OUTLINE: Patients are stratified according to the availability of suitable reactive cells (peripheral blood lymphocytes [PBL] vs tumor-infiltrating lymphocytes [TIL]).

Autologous lymphocyte activation and expansion: Autologous PBL or TIL are activated in vitro with gp100:209-217 (210M) antigen (gp100) and expanded.
Lymphocyte-depleting nonmyeloablative preparative regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 15-30 minutes on days -5 to -1.
Autologous lymphocyte infusion: Autologous PBL or TIL are reinfused over 20-30 minutes on day 0*. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 1 or 2 and continuing until blood counts recover.
Fowlpox vaccine administration: Patients receive recombinant fowlpox virus encoding gp100 peptide IV over 1-2 minutes on days 2 and 28 (if treated with high-dose aldesleukin [IL-2], as below) OR days 2 and 43 (if treated with low-dose IL-2, as below).
IL-2 therapy: Patients receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0*-4 (beginning within 24 hours after lymphocyte infusion) and 28-32 OR low-dose IL-2 SC on days 0*-4 (beginning within 24 hours after lymphocyte infusion), 7-11, 14-18, 21-25, 28-32, 35-39, 50-54, 57-61, 64-68, 71-75, 78-82, and 85-89.

NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.

Patients are evaluated between days 72-86 (if treated with high-dose IL-2) OR days 98-123 (if treated with low-dose IL-2). Patients with stable disease or a minor, mixed, or partial response may receive up to 2 retreatment courses as above. Patients with progressive disease after IV lymphocyte infusion may be retreated with intra-arterial lymphocytes along with all other agents outlined above.

After completion of study treatment, patients are followed at 2-4 weeks (if treated with high-dose IL-2) OR at 3 weeks (if treated with low-dose IL-2) and then annually thereafter.

PROJECTED ACCRUAL: A total of 68 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 melanoma
- Metastatic disease
Refractory to OR relapsed after standard therapy (including high-dose aldesleukin [IL-2])
Measurable disease
HLA-A*0201 positive
gp100-reactive cells
Symptomatic CNS lesions requiring immediate active treatment allowed after treatment of symptomatic lesions

PATIENT CHARACTERISTICS:

Age

16 and over

Performance status

ECOG 0-1

Life expectancy

At least 3 months

Hematopoietic

Absolute neutrophil count > 1,000/mm^3 (without support of filgrastim [G-CSF])
Platelet count > 100,000/mm^3
Hemoglobin > 8.0 g/dL (transfusion allowed)
Lymphocyte count > 500/mm^3
No coagulation disorders

Hepatic

AST and ALT < 3 times upper limit of normal
Bilirubin ≤ 2.0 mg/dL (<3.0 mg/dL in patients with Gilbert's syndrome)
Hepatitis B surface antigen negative
Hepatitis C virus antibody negative

Renal

Creatinine ≤ 2.0 mg/dL

Cardiovascular

No major medical illness of the cardiovascular system
No myocardial infarction
No cardiac arrhythmias
Negative stress thallium or comparable test
LVEF > 45%* NOTE: *Required for patients who are age 50 and over OR who have a history of EKG abnormalities, symptoms of cardiac ischemia, or arrhythmias AND who receive high-dose IL-2 as a part of study treatment

Pulmonary

No major medical illness of the respiratory system
No obstructive or restrictive pulmonary disease
FEV_1 > 60% of predicted* NOTE: *Required for patients who have a prolonged history of cigarette smoking or symptoms of respiratory dysfunction AND who receive high-dose IL-2 as a part of study treatment

Immunologic

HIV negative
No major medical illness of the immune system
No primary or secondary immunodeficiency
No active systemic infection
No opportunistic infections
No allergy to eggs or any known hypersensitivity to any study agents

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 4 months after study participation
Willing to complete a durable power of attorney (DPA)

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

Recovered from prior chemotherapy
At least 6 weeks since prior nitrosoureas

Endocrine therapy

No concurrent systemic steroid therapy

Radiotherapy

Recovered from prior radiotherapy

Surgery

Prior minor surgery within the past 3 weeks allowed provided all toxic effects have resolved to ≤ grade 1

Other

At least 4 weeks since prior systemic therapy and recovered

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084500

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

Principal Investigator:

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:	CDR0000365316, NCI-04-C-0152, NCI-6585
Study First Received:	June 10, 2004
Last Updated:	December 13, 2008
ClinicalTrials.gov Identifier:	NCT00084500
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent melanoma
stage IV melanoma

Study placed in the following topic categories:

Cyclophosphamide
Fludarabine monophosphate
Recurrence
Melanoma
Neuroendocrine Tumors
Virus Diseases
Neuroectodermal Tumors

Aldesleukin
Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Neuroepithelioma
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
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