Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	CCF-RPC-3209 NCI-T89-0218O, T89-0218

Objectives

I.  Perform a Phase II trial of tumor infiltrating lymphocytes (TIL) 
administered with continuous infusion interleukin-2 (IL-2) in patients with 
metastatic renal cell carcinoma, following TIL expansion in vitro with IL-2 
and interleukin-4 (IL-4) and restimulation with autologous tumor cells.
II.  Characterize the phenotypes, cytolytic potency, and specificity of the 
effector cell population in the expanded TIL.
III.  Characterize the phenotype and lytic activity of lymphocytes in 
metastatic lesions of treated patients.
IV.  Determine, using indium-111 labeling, the in vivo distribution of TIL 
expanded in vitro with IL-4/IL-2.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients at least 18 years of age 
with histologically confirmed metastatic renal cell carcinoma that is 
surgically incurable; the primary tumor or a metastatic lesion must have been 
removed for TIL preparation, and objectively measurable disease must be 
present.  The tumor burden must be minimal, as defined by all of the following 
criteria:  postnephrectomy status (patients with unresected primary renal cell 
carcinoma who are otherwise eligible for this study undergo nephrectomy prior 
to entry; if there are liver metastases, no more than 30% of the liver 
involved as determined on CT scan; if there are osseous matastases, calcium no 
higher than 11.0 mg/dl; and no CNS metastases as confirmed by CT scan of the 
head.  No restrictions apply to pulmonary metastases.  No prior chemotherapy 
or therapy with interleukin-2 or interleukin-4 is allowed.  Radiotherapy for 
control of pain from skeletal lesions is allowed but must have been completed 
at least 4 weeks prior to entry.  At least 14 days must have elapsed since 
prior surgery.  An ECOG performance status of 1 or better and a life 
expectancy of at least 3 months are required, as are the following indicators 
of adequate organ function:  hemoglobin at least 10.0 g/dl, WBC at least 
4,000, and platelets at least 100,000; bilirubin no more than 1.5 mg/dl; 
creatinine no more than 1.8 mg/dl or creatinine clearance (measured or 
calculated) at least 60 ml/minute; and DLCO at least 50%.  There must be no 
history of CHF, myocardial infarction, angina, or serious cardiac arrhythmia 
(NYHA class must be II or better); a left ventricular ejection fraction of at 
least 50% is required.  The following conditions exclude:  active infection 
requiring antibiotics within the 3 weeks prior to entry, contraindication to 
the use of pressor agents, significant effusions and/or ascites, requirement 
for corticosteroids, positive HTLV-III antibody test (ELISA) or positive 
HBsAg, and history of malignant hyperthermia.  There must be no history of a 
second malignancy other than basal cell carcinoma of the skin or carcinoma in 
situ of the cervix unless the patient has been off therapy and disease free 
for at least 5 years.  Fertile women must have a negative pregnancy test and 
be using an effective method of contraception.

Expected Enrollment

If at least 1 response is seen in the first 14 patients entered, a total of 25 
evaluable patients will be studied.  It is anticipated that 1-2 patients/month 
will be entered.  The study should be completed within 12 months.

Outline

Nonrandomized study.  Eligible patients with unresected primaries will undergo 
nephrectomy prior to protocol treatment.
Biological Response Modifier Therapy.  Tumor Infiltrating Lymphocytes, TIL, 
expanded in vitro with Interleukin-2, IL-2, NSC-600664 and Interleukin-4, 
IL-4, NSC-620211 and restimulated with autologous tumor cells; plus IL-2.

Trial Contact Information

Trial Lead Organizations

Cleveland Clinic Foundation Hospital

Ronald Bukowski, MD, Protocol chair		Ph: 216-444-6825; 800-862-7798