|Phase 1Phase 2||
- Ages Eligible for Study
- 18 years and up
- Genders Eligible for Study
Renal Cancer, Immunotherapy, Clinical Response, Toxicity, Gene Therapy, and Kidney Cancer
- National Cancer Institute (NCI)
1. Measurable metastatic clear cell renal cancer. Histologic diagnosis will be
confirmed by the Laboratory of Pathology at the NCI.
2. Patients must have previously received at least one systemic standard care
regimens and have progressed or be found to be intolerant of standard therapies.
3. Greater than or equal to 18 years of age.
4. Willing to sign a durable power of attorney
5. Able to understand and sign the Informed Consent Document
6. Clinical performance status of ECOG 0 or 1.
7. Life expectancy of greater than three months.
8. Patients of both genders must be willing to practice birth control during and
for four months after receiving the preparative regimen.
1. Seronegative for HIV antibody. (The experimental treatment being evaluated
in this protocol depends on an intact immune system. Patients who are HIV
seropositive can have decreased immunecompetence, and thus be less
responsive to the experimental treatment and more susceptible to its
2. Seronegative for hepatitis B antigen and hepatitis C antibody unless
3. Women of child-bearing potential must have a negative pregnancy test
because of the potentially dangerous effects of the preparative
chemotherapy on the fetus.
1. Absolute neutrophil count greater than or equal to 1000/mm3 without the
support of filgrastim.
2. WBC greater than or equal to 3000/mm3.
3. Platelet count greater than or equal to 100,000/mm3.
4. Hemoglobin greater than or equal to 8.0 g/dl.
1. Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
2. Serum creatinine less than or equal to 1.6 mg/dl.
3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with
Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
12. More than four weeks must have elapsed since any prior systemic therapy at the
time the patient receives the preparative regimen, and patients' toxicities must
have recovered to a grade 1 or less (except for alopecia or skin rash, which
must have recovered to a grade 2 or less).
13. Patients who have previously received anti-CTLA4 antibody must have a normal
colonoscopy with normal colonic biopsies.
1. Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
2. Active systemic infections; coagulation disorders or other major medical illnesses of
the cardiovascular, respiratory or immune system; myocardial infarction; cardiac
arrhythmias; obstructive or restrictive pulmonary disease.
3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
4. Concurrent opportunistic infections (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who have decreased immune
competence may be less responsive to the experimental treatment and more susceptible
to its toxicities.)
5. Concurrent systemic steroid therapy
6. History of severe immediate hypersensitivity reaction to any of the agents used in
7. History of coronary revascularization or ischemic symptoms
8. Documented LVEF less than or equal to 45%. LVEF will be evaluated in patients with:
1. History of ischemic heart disease, chest pain, or clinically significant atrial
and/or ventricular arrhythmias including but not limited to: atrial
fibrillation, ventricular tachycardia, second or third degree heart block
2. Age greater than or equal to 60 years old
9. Documented FEV1 less than or equal to 60% predicted. Screening pulmonary function
testing will be done in patients with:
1. A prolonged history of cigarette smoking (20 pk/year of smoking, who have not
quit within the past 2 years).
2. Symptoms of respiratory dysfunction
10. Patients who have a history of more than two CNS metastases.
11. Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter
or shows significant surrounding edema on MRI scan will not be eligible until they
have been treated and demonstrated no clinical or radiologic CNS progression for at
least 2 months.
Background: - An experimental cancer treatment procedure involves taking a patient's own tumor or blood cells, modifying them with a gene that targets proteins on the surface of tumor cells, and growing those cells in a laboratory. The modified cells are then given back to the patient by intravenous (IV) transfusion, in the hope that the new cells will attack and destroy the cancer cells without harming healthy tissue. - This procedure has been used for melanoma patients, and researchers are now attempting to use this treatment for patients with renal (kidney) cancer. In the laboratory, this attack kills nearly all kidney cancers tested, but not normal tissues. However, the effectiveness and possible side effects of this treatment are still being studied. Objectives: - To find out if cells modified to target DR4 and TRAIL (two proteins found on the surface of many kidney tumors) are effective in treating kidney cancer. - To determine the maximum tolerated dose (the highest dose that does not cause unacceptable side effects) of the modified cells. Eligibility: - Patients 18 years of age and older with metastatic renal cancer whose disease has not responded to standard treatment. - Patients will be divided into two study branches: Arm A for those who will be receiving modified cells from their biopsied tumor, and Arm B for those who will be receiving their own modified white blood cells. Design: - Five-stage treatment process, outpatient for stages 1 and 5 and inpatient for stages 2 through 4: - Work-up (1 to 2 weeks): Physical examination, heart and lung function tests, imaging tests, blood and/or tumor samples taken. - IV chemotherapy (1 week): Cyclophosphamide and fludarabine to prepare for the new cell infusion. - IV cell infusion and treatment with IL-2 to support the modified cells (4 days). - Recovery (1 to 2 weeks): Recover from effects of chemotherapy and infusion. - Follow-up (every 1 to 6 months): Return to clinic for physical exam, review of side effects, other tests. - Follow-up evaluations will continue to determine the success of the treatment. - Evaluations during the treatment period: - Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant. - Blood and urine tests. - Disease evaluation and monitoring on both inpatient and outpatient basis. - Because researchers do not know the long-term side effects of gene therapy, patients will be asked to participate in long-term follow up for up to 15 years. The follow-up will involve yearly physical exams and medical history, and blood collection (3, 6 and 12 months after treatment, and every year after that).
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00923390
National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland United States(Recruiting)