Cultured White Cells Plus Interleukin-2 to Treat Advanced Kidney Cancer
Cultured White Cells Plus Interleukin-2 to Treat Advanced Kidney Cancer
Background:

 -  Some patients with advanced kidney cancer have immune cells that can recognize and kill
 their cancer, but the cells are not active enough or numerous enough to accomplish this
 on their own.

 -  In recent studies of patients with advanced melanoma, some patients given special
 tumor-fighting cells (cells taken from the patient's tumor cells and grown in the
 laboratory) showed some anti-tumor response.

 Objectives:

 -To determine whether special tumor-fighting cells taken from the patient's blood or tumor
 and grown in the laboratory can cause tumors in patients with kidney cancer to shrink when
 they are given back to the patient along with interleukin-2.

 Eligibility: Patients 18 years of age or older with advanced kidney cancer.

 Design:

 -  Up to 29 patients will be treated in this study.

 -  Patients undergo tumor biopsy to collect tumor cells for creating special tumor-fighting
 cells for later infusion.

 -  Patients undergo apheresis to collect stem cells for later re-infusion. For apheresis,
 whole blood is collected through a needle in an arm vein and circulated through a
 cell-separating machine where the stem cells are extracted. The rest of the blood is
 returned through the same needle or a needle in the other arm.

 -  Before receiving the treated white cells, patients are given two drugs to suppress the
 immune system so the treated cells can work without interference from immune system
 cells. They are given cyclophosphamide over 2 days through a catheter (plastic tube
 inserted into a vein in the arm or neck) and fludarabine through the catheter over 15-30
 minutes for the next 5 days.

 -  The day after the last dose of fludarabine, the tumor-fighting cells are infused through
 a vein over 10-20 minutes.

 -  Following the cell infusion, patients start treatment with high-dose interleukin-2 every
 8 hours for a maximum of 12 doses.

 -  Patients are evaluated with x-ray studies about 1 month after receiving the cells and
 interleukin 2 (IL-2) to look for tumor response to treatment. Those who show significant
 improvement continue to receive treatment until the treated cells are used up or the
 patient no longer benefits or develops unacceptable side effects.
Background:

 One area of therapeutic advancement in immunotherapy has been to identify autologous
 tumor-reactive T-cells and expand them in vitro, and administer them in adoptive transfer
 back to patients. These T-cells have been obtained either from tumor infiltrating lymphocytes
 (TIL) which appear enriched for tumor-reactive T-cells or by in vitro stimulation of
 peripheral blood T-cells from cancer patients. Recent success in patients with melanoma has
 in large part been due to a T-cell expansion protocol described by Riddell et al. using
 anti-CD3 (cluster of differentiation 3) and irradiated allogeneic feeder cells and the use of
 conditioning chemotherapy prior to cell transfer. This current study uses the results of
 these Surgery Branch adoptive cell therapy trials to study their potential in patients with
 metastatic renal cell cancer.

 Objectives:

 The primary objective will be to determine whether adoptive lymphocyte transfer in
 conjunction with preparative lympho-depletion chemotherapy and interleukin-2 (IL-2) may
 result in clinical tumor regression in patients with metastatic renal cancer.

 Eligibility:

 Patients with metastatic renal cell cancer who have failed conventional therapy with
 interleukin-2, from whom tumor-reactive lymphocytes (from either peripheral blood, lymph
 nodes or tumor-infiltrating lymphocytes) can be obtained and expanded in vitro.

 Patients must meet specific safety laboratory criteria, be able to tolerate interleukin 2
 (IL-2), and have no concurrent major medical illnesses or symptomatic brain metastases.

 Design:

 All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of
 cyclophosphamide (60 mg/kg/day intravenous (IV)) on days -7 and -6 and fludarabine (25
 mg/m^2/day intravenous (IV)) on days -5 through -1. On day 0 patients will receive an
 infusion of their own tumor-reactive T cells grown in vitro (greater than or equal to 5x10^8
 cells for a cycle) and then begin high-dose IL-2 (720,000 IU/kg intravenous (IV) every 8
 hours for up to 15 doses).

 Clinical and Immunologic response will be evaluated about 3 to 5 weeks after the treatment
 regimen.

 This trial will be conducted as a phase II trial using a two-stage MinMax design which will
 try to determine whether intravenous (IV) cell administration can produce a modest response
 rate targeted to be greater than or equal to 35 % (p1=0.35) as opposed to an undesirably low
 response rate of less than 15% (p0=0.15). If at least 3 patients of 15 have an objective
 response (partial response (PR) or complete response (CR)) accrual will proceed to 28
 patients, with a projected accrual over three years.
-  INCLUSION CRITERIA: CELL HARVEST:

 -  Patients must have metastatic renal cell cancer.

 -  age greater than or equal to 18 years.

 -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 at entry
 to the trial.

 -  Life expectancy of greater than three months.

 -  Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental
 treatment being evaluated in this protocol depends on an intact immune system.
 Patients who are human immunodeficiency virus (HIV) seropositive can have decreased
 immune competence and can thus be less responsive to the experimental treatment and
 more susceptible to it's toxicities.)

 -  Seronegative for hepatitis B antigen.

 -  Seropositive for Epstein-Barr Virus (EBV).

 -  Patients with electrocardiogram (EKG) abnormalities, symptoms of cardiac ischemia or
 arrythmias or age greater than 50 years must have a normal stress cardiac test (stress
 thallium, stress multi-gated acquisition scan (MUGA), dobutamine echocardiogram or
 other stress test).

 -  Patients who have a recent prolonged history of cigarette smoking or symptoms of
 respiratory dysfunction must have pulmonary function testing with an forced expiratory
 volume in 1 second (FEV(1)) greater than 60% predicted.

 EXCLUSION CRITERIA: CELL HARVEST:

 -Active systemic infections, coagulation disorders, contra-indications to receiving
 interleukin-2 (IL-2) or major medical illnesses of the cardiovascular, respiratory or
 immune system.

 INCLUSION CRITERIA: CELL INFUSION:

 -  Patients must have measurable metastatic renal cell cancer and have tumor progression
 after therapy with interleukin-2 (IL-2).

 -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 at entry
 to the treatment phase of this trial.

 -  Platelet count greater than 100,000/mm^3.

 -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three
 times the upper limit of normal.

 -  Serum creatinine less than or equal to 1.6 mg/dl.

 -  Total bilirubin less than or equal to 1.6 mg/dl or direct bilirubin less than or equal
 to 0.5 mg/dl.

 -  Life expectancy of greater than three months.

 -  At the time of T-cell transfer, the patient must have a T-cell population which has
 met the attached Certificate of Analysis for tumor recognition and safety testing.

 -  Any patient receiving interleukin-2 (IL-2) must sign a durable power of attorney.

 -  Male and Female patients must be willing to practice contraception during the
 treatment phase of this study..

 -  Patients with asymptomatic brain metastases may be considered eligible.

 EXCLUSION CRITERIA: CELL INFUSION:

 -  Potentially effective therapy for renal cell cancer (RCC) within four weeks of the
 time the patient receives T-cell transfer (with the exception of local irradiation to
 non-evaluated sites).

 -  Requirement for steroid therapy.

 -  Active systemic infections, coagulation disorders, contra-indications to receiving
 interleukin-2 (IL-2) or major medical illnesses or the cardiovascular, respiratory or
 immune system.

 -  Pregnant patients and nursing mothers will be excluded because of the unknown effects
 of this therapy on the fetus or nursing infant.