Vaccine Therapy With or Without Fludarabine in Treating Patients With Stage IV Kidney Cancer

Sponsor

St. Luke's Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT00093522

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

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

PURPOSE: This randomized phase II trial is studying vaccine therapy and fludarabine to see how well they work compared to vaccine therapy alone in treating patients with stage IV kidney cancer.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Biological: autologous tumor cell vaccine Biological: keyhole limpet hemocyanin Biological: therapeutic autologous dendritic cells Drug: fludarabine phosphate Procedure: conventional surgery	Phase 2

Detailed Description

OBJECTIVES:

Primary

Compare the safety of vaccination comprising autologous dendritic cells loaded with autologous tumor lysate and keyhole limpet hemocyanin with vs without non-myeloablative fludarabine in patients with stage IV renal cell carcinoma.
Compare, preliminarily, the efficacy of these regimens in these patients.
Compare the overall survival of patients treated with these regimens.

Secondary

Determine whether this vaccine induces tumor-reactive peripheral T-cell responses or delayed-type hypersensitivity in these patients.

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

All patients undergo surgery to remove tumor at metastatic sites to generate autologous tumor lysate. Patients then undergo leukapheresis to obtain peripheral blood mononuclear cells for the generation of dendritic cells (DC). The DC are then exposed to autologous tumor lysate and keyhole limpet hemocyanin (KLH).

Arm I: Three weeks after leukapheresis, patients receive vaccination comprising DC loaded with autologous tumor lysate and KLH (DC vaccine) intradermally once every 14 days for a total of 4 injections in the absence of disease progression or unacceptable toxicity.
Arm II: Two weeks after leukapheresis, patients receive fludarabine IV over 15-30 minutes once daily for 3 days. Beginning approximately 5 weeks after leukapheresis, patients also receive DC vaccine as in arm I.

Patients are followed at 1, 3, and 7-9 weeks, at 4, 6, 9, and 12 months, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 28 patients (14 per treatment arm) will be accrued for this study within 2-3 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Phase II Pilot Study of Tumor-Loaded Dendritic Cells Alone or Following a Non-Myeloablative Conditioning Regimen in Patients With Metastatic Renal Cell Carcinoma

Study Start Date :

Aug 1, 2004

Outcome Measures

Primary Outcome Measures

Safety as measured by NCI common toxicity table at completion of study []
Response as measured by RECIST guidelines and the Kaplan-Meier method at 5 years []
Survival as measured by the Kaplan-Meier method at 5 years []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed renal cell carcinoma
Stage IV disease
Received no benefit from standard therapy OR ineligible for standard therapy OR declined standard therapy
At least 1 site of metastatic disease that can be surgically removed AND at least 1 site of metastatic disease than can remain in the patient (indicator lesion) after surgery
Total volume of the site or sites of disease to be surgically removed must be > 2.0 cm^3
Unidimensionally measurable disease
At least 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
No brain metastasis

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

More than 6 months

Hematopoietic

WBC ≥ 3,000/mm^3
Platelet count ≥ 75,000/mm^3
Hemoglobin ≥ 10 g/dL

Hepatic

SGPT and SGOT ≤ 2.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
Hepatitis C antibody negative
Hepatitis B surface antigen negative

Renal

Creatinine ≤ 1.5 times ULN
Creatinine clearance > 40 mL/min

Cardiovascular

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

Immunologic

Coomb's test negative
HIV-1 and -2 negative
No active infection
No unexplained fever (temperature > 100.5° F or 38.1°C)
No lymphocytopenia
No hypogammaglobulinemia
No autoimmune disease or other immunocompromising condition that would preclude study participation
No history of impaired immune response
No history of tuberculosis OR positive PPD skin test
No history of allergic reaction attributed to compounds of similar biological composition to study vaccine
No history of allergic reaction to antibiotics

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 1 month after study participation
No psychiatric illness or social situation that would preclude study participation
No other malignancy within the past 5 years except resected basal cell carcinoma or carcinoma in situ of the cervix
No other concurrent illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

More than 4 weeks since prior immunotherapy

Chemotherapy

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

At least 4 weeks since prior steroid therapy or steroid-containing compounds
At least 2 weeks since prior topical or inhaled steroids

Radiotherapy

More than 4 weeks since prior radiotherapy

Surgery

See Disease Characteristics

Other

More than 4 weeks since prior investigational agents
More than 1 week since prior antibiotics
No concurrent renal dialysis
No concurrent anticoagulants
No other concurrent anticancer agents or therapies
No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Midwest Heart Surgery Institute, Limited	Milwaukee	Wisconsin	United States	53215
2	Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215