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

Melanoma (Skin) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00091143
• Other study ID #: CDR0000383908
• Secondary ID: PPMC-IRB-02-99NC
• Status: Completed
• Phase: Phase 1
• First received: September 7, 2004
• Last updated: April 2, 2013
• Start date: July 2004
• Est. completion date: March 2010

Study information

• Verified date: August 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• gp100 antigen

• incomplete Freund's adjuvant

• keyhole limpet hemocyanin

Drug:
• fludarabine phosphate

Procedure:
• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Providence Cancer Center, Earle A. Chiles Research Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity by clinical and laboratory observation at 1 month			Yes
Primary	Antigen-specific T-cell responses by tetramer analysis, ELISPOT, and cytokine flow cytometry periodically			No
Secondary	Compare 2 different dosing schedules of fludarabine in terms of lymphocyte recovery using a complete blood count periodically			No
Secondary	Tumor regression by standard imaging at study completion			No