Fludarabine Followed by Vaccine Therapy and White Blood Cell Infusions in Treating Patients With Unresectable or Metastatic Melanoma - Full Text View

Sponsors and Collaborators:	Providence Cancer Center, Earle A. Chiles Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00091143

Purpose

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Infusions of a person's white blood cells may be able to replace immune cells that were destroyed by chemotherapy. Combining fludarabine with vaccine therapy and white blood cell infusions may kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects of giving vaccine therapy together with fludarabine and white blood cell infusions and to see how well it works in treating patients with unresectable or metastatic melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Drug: fludarabine phosphate Drug: gp100 antigen Drug: incomplete Freund's adjuvant Drug: keyhole limpet hemocyanin Procedure: peripheral blood stem cell transplantation	Phase I

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Fludarabine Fludarabine monophosphate Freund's adjuvant Montanide ISA 51

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Pilot Trial of Therapeutic Vaccination With a Modified gp100 Melanoma Peptide (gp100:209-217(210M)), Montanide ISA 51, and KLH With Reconstitution After Chemotherapy to Induce Lymphopenia in Patients With Metastatic Melanoma

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

Primary Outcome Measures:

Toxicity by clinical and laboratory observation at 1 month [ Designated as safety issue: Yes ]
Antigen-specific T-cell responses by tetramer analysis, ELISPOT, and cytokine flow cytometry periodically [ Designated as safety issue: No ]

Secondary Outcome Measures:

Compare 2 different dosing schedules of fludarabine in terms of lymphocyte recovery using a complete blood count periodically [ Designated as safety issue: No ]
Tumor regression by standard imaging at study completion [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	July 2004
Estimated Primary Completion Date:	May 2005 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the toxicity and immune effects of vaccination comprising modified gp100 peptide (gp100:209-217[210M]), Montanide ISA-51, and keyhole limpet hemocyanin followed by peripheral blood mononuclear cell reinfusion after treatment-induced lymphopenia with fludarabine in patients with unresectable or metastatic melanoma.
Determine the induction of antigen-specific T-cell responses in patients treated with this regimen.
Determine the kinetics and duration of immune response in patients treated with this regimen.
Compare the immunologic effects of this regimen in these patients with historical results.

Secondary

Compare 2 different dosing schedules of fludarabine, in terms of induction of lymphopenia and granulocytopenia and on the induction of a specific immune response to this vaccine, in these patients.

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

Within 2 weeks before the start of fludarabine, all patients undergo leukapheresis over 4-6 hours for the collection of peripheral blood mononuclear cells (PBMCs).

Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5.
Arm II: Patients receive fludarabine as in arm I on days 1, 3, and 5. In both arms, patients receive autologous PBMCs IV over approximately 30 minutes on day 8 and vaccination comprising gp100:209-217(210M) peptide, Montanide ISA-51, and keyhole limpet hemocyanin subcutaneously on days 8, 22, 36, 50, and 64. Patients with stable or responding disease continue to receive vaccination on day 78 and then every 28-31 days for up to 1 year.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 20 patients (10 per treatment arm) will be accrued for this study within 2 years.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed malignant melanoma
- Metastatic or unresectable disease
Measurable disease
HLA-A2 positive
Received at least 1 prior immunotherapy and/or chemotherapy regimen for metastatic disease (first 6 patients only)
No known brain metastases unless previously treated with radiotherapy and/or surgery AND is stable for at least 1 month after treatment

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

More than 3 months

Hematopoietic

WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Absolute lymphocyte count ≥ 500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10 g/dL (transfusions allowed)
Hematocrit ≥ 24%
No other active bleeding

Hepatic

Bilirubin < 2 times upper limit of normal (ULN) (unless due to Gilbert's disease)
AST and ALT < 3 times ULN
Hepatitis B surface antigen negative
Hepatitis C antibody negative

Renal

Creatinine < 2 mg/dL
No uncontrolled hypercalcemia

Cardiovascular

No uncontrolled symptomatic congestive heart failure
No unstable angina pectoris
No uncontrolled cardiac arrhythmia
No uncontrolled hypertension

Pulmonary

No uncontrolled bronchospasm
No hemoptysis

Immunologic

Negative serology for all of the following:
- HIV-1 and HIV-2
- HTLV-1 and -2
- Syphilis
Rheumatoid factor < 43 units/μL
Anti-nuclear antibody < 11 units/μL
No history of multiple sclerosis, systemic lupus erythematosus, or myasthenia gravis
No primary or secondary immunodeficiency
No active infection
No allergy to seafood or shellfish that would preclude study participation

Other

No active gastrointestinal bleeding
No uncontrolled hyperglycemia
No other medical or psychiatric condition or social situation that would preclude study compliance
No other uncontrolled illness
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3-4 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
No prior immunization with gp100:209-217(210M) peptide

Chemotherapy

See Disease Characteristics
More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

More than 2 weeks since prior steroid therapy except replacement steroids or inhaled steroids
No concurrent corticosteroids except replacement steroids
No concurrent dexamethasone

Radiotherapy

See Disease Characteristics
More than 2 weeks since prior radiotherapy

Surgery

See Disease Characteristics
Recovered from prior surgery

Other

No other concurrent investigational agents
No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00091143

Locations

United States, Oregon
Providence Cancer Center at Providence Portland Medical Center	Recruiting
Portland, Oregon, United States, 97213-2967
Contact: Clinical Trials Office - Providence Cancer Center at Providenc 503-215-6412

Sponsors and Collaborators

Providence Cancer Center, Earle A. Chiles Research Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Walter J. Urba, MD, PhD

Providence Cancer Center, Earle A. Chiles Research Institute

More Information

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

Study ID Numbers:	CDR0000383908, PPMC-IRB-02-99, NCI-6361
Study First Received:	September 7, 2004
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00091143
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent melanoma
stage III melanoma
stage IV melanoma

Study placed in the following topic categories:

Lymphopenia
Fludarabine monophosphate
Keyhole-limpet hemocyanin
Recurrence
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors

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

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue

Physiological Effects of Drugs
Adjuvants, Immunologic
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Nevi and Melanomas

ClinicalTrials.gov processed this record on January 14, 2009