INCLUSION CRITERIA: Recipient
Diagnosis of metastatic renal cell carcinoma, either clear cell type or non-clear cell type. The diagnosis must be confirmed by the Laboratory of Pathology of NCI or Hackensack (there will be no central pathology review).
Subject must be status-post nephrectomy (either partial or complete resection).
The consent process will include a discussion of the potential role of high-dose IL-2 therapy prior to protocol enrollment. High-dose IL-2 therapy is not widely available, but may be available on an NCI protocol (Dr. Yang) or through Dr. Alter for Hackensack patients. IL-2 therapy may also be administered by any other qualified physician; the Novartis web-site has a list of such physicians. For subjects who are deemed to be eligible for high-dose IL-2 and elect to receive this therapy, such subjects must have progressive disease post-IL-2 to enter this study; such subjects must also have received and have had progressive disease after therapy with one of the agents listed below.
Subject must have progressive disease after therapy consisting of one of the following FDA-approved agents: sorafenib, sunitib, or temsirolimus.
Patients 18 - 75 years of age. Subjects older than 75 will not be enrolled due to an increased rate of transplant-related complications.
Must have consenting sibling matched at 6/6 HLA antigens (A, B, DR).
Patient or legal guardian must be able to give informed consent.
All previous therapy must be completed at least 2 weeks prior to study entry. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less.
Karnofsky performance status greater than or equal to 80%.
Life expectancy of at least 3 months.
Left ventricular ejection fraction greater than 40% (MUGA or echo) within 28 days of enrollment.
DLCO greater than 50% of expected value (Hb corrected), obtained within 28 days of enrollment.
Creatinine clearance greater than or equal to 40 ml/min. Creatinine clearance will be determined by testing of a 24 hour urine collection and simultaneous serum creatinine value. In previous studies, the creatine clearance of patients with metastatic renal cell cancer who underwent nephrectomy was 53 plus or minus 19.
Serum total bilirubin less than 2.5 mg/dl, and serum ALT and AST values less than or equal to 2.5 times the upper limit of normal. ALT and AST values above these levels may be accepted (up to a maximum of 5 times the upper limit of normal), at the discretion of the PI or study chairperson, if such elevations are thought to be due to liver involvement by malignancy.
INCLUSION CRITERIA : Donor
Sibling who is 6/6 HLA-matched with recipient.
Ability to give informed consent.
Age 18 years to 80 years. Donors older than 80 will not be eligible due to potentially increased complications from the donation procedure.
Adequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis.
Donors must be HIV negative, hepatitis B surface antigen negative, and hepatitis C antibody negative. This is to prevent the possible transmission of these infections to the recipient. Donors with a history of hepatitis B or hepatitis C infections may be eligible. However, eligibility determination of such patients will require a hepatology consultation. The risk/benefit of the transplant and the possibility of transmitting hepatitis will be discussed with the patient and eligibility will then be determined by the prinicipal investigator.
A donor who is lactating must substitute formula feeding for her infant during the period of cytokine administration. Filgrastim may be secreted in human milk, although its bioavailability from this source is not known. Limited clinical data suggest that administration of filgrastim or to neonates is not associated with adverse outcomes.
EXCLUSION CRITERIA: Recipient
Active infection that is not responding to antimicrobial therapy.
Active CNS involvement by malignancy.
HIV infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.
Chronic active hepatitis B. Patient may be hepatitis B core antibody positive. For patients with concomitant positive hepatitis B surface antigen, patient will require a hepatology consultation. The risk/benefit profile of transplant and hepatitis B will be discussed with the patient and eligibility determined by the principal investigator and protocol chairperson.
Hepatitis C infection. Patient may have hepatitis C infection. However, each patient will require a hepatology consultation. The risk/benefit profile of transplant and hepatitis C will be discussed with the patient and eligibility determined by the principal investigator and protocol chairperson.
Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception from the time of study entry to at least one year post-transplant; effective methods include intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation/hysterectomy, partner's vasectomy, or barrier methods (condom, diaphragm, or cervical cap). Males on the protocol, and their partners of child-bearing potential, must also use an effective form of contraception at study entry and for one year post-transplant. The effects of the chemotherapy, the subsequent transplant, and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant; therefore, women should not breastfeed during the interval from study entry to one year post-transplant.
History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent (as determined by principal investigator or study chairman).
EXCLUSION CRITERIA: Donor
History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
History of hypertension that is not controlled by medication, stroke, or severe heart disease. Individuals with symptomatic angina will be considered to have severe heart disease and will not be eligible to be a donor.
No other medical contraindications to stem cell donation (i.e. severe atherosclerosis, autoimmune disease, iritis or episcleritis, deep venous thrombosis, cerebrovascular accident). Patients with a history of coronary artery bypass grafting or angioplasty will receive a cardiology evaluation and be considered on a case-by-case basis.
History of prior malignancy. However, cancer survivors who have undergone potentially curative therapy may be considered for stem cell donation on a case-by-case basis. The risk/benefit of the transplant and the possibility of transmitting viable tumor cells at the time of transplantation will be discussed with the patient.
Donors must not be pregnant. The effects of cytokine therapy on a fetus are unknown. Donors of childbearing potential must use an effective method of contraception from the time of study entry until at least one year post-transplant.
Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000 per microliliter).
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/13/2009