• Determine the best rate of tumor response of complete response (CR) + complete unconfirmed response (CRU) + partial response (PR) within 6 months after matched unrelated donor (MUD) nonmyeloablative stem cell transplantation (NST) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  

• Overall survival after MUD NST [ Time Frame: Two years ] [ Designated as safety issue: Yes ]
  
• Rate of complete donor myeloid and lymphoid chimerism after MUD NST [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  
• Incidence and severity of acute and chronic graft-versus-host disease (GvHD) after MUD NST [ Time Frame: Two years ] [ Designated as safety issue: Yes ]
  
• Incidence of treatment-related mortality (TRM) [ Time Frame: 100 Days ] [ Designated as safety issue: Yes ]
  
• Assess cytotoxic T-lymphocyte reactivity [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  
• Assess antibody activity against potential tumor antigenic peptides in graft-versus-renal cell carcinoma (RCC) effect [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
  

Procedure: NST using MUD for metastatic renal cell carcinoma

Preparative regimen:

Fludarabine 25 mg/m2 IV once a day x 5 days (-6,-5,-4,-3,-2) Melphalan 70 mg/m2 IV once a day x 2 days (-3,-2) Donor Stem Cell Infusion: Stem cells will be infused on day 0 GVHD prophylaxis: Tacrolimus and methotrexate 5 mg/m2 IV day 1, 3, 6 and 11

Standard treatment for kidney cancer that has spread to other parts of the body may include immunotherapy (a therapy that uses the body's natural immune system to fight cancer) and cytokines (proteins found in the body). If these treatments are not successful at controlling the cancer then chemotherapy or thalidomide are used. Chemotherapy and thalidomide will not cure kidney cancer but they may control the disease in some patients.

In some patients, transplants are now proposed for study. Stem cells (from bone marrow or the bloodstream) are normally used to treat cancers of the blood, not kidney cancer. Since researchers are still learning about using stem cell transplants for kidney cancer, the study is considered a research study. Patients participating in this study will receive smaller doses of chemotherapy drugs to prepare them for the transplant than patients who have a standard transplant. This type of transplant is called a "reduced intensity" transplant. A reduced intensity transplant uses the cell-killing activity of the transplanted donor stem cells to attack the recipient's cancer cells. This is called graft-versus-tumor-effect (GVT). Previous studies have shown that GVT may be greater if the donor is not related to the recipient.

Inclusion Criteria:

• Diagnosis of metastatic (stage IV) renal cell carcinoma (RCC) predominately clear cell type
• Prior nephrectomy
• Available HLA-matched (8/8, 7/8) unrelated donor
• At least one prior immunotherapy; or immunotherapy + chemotherapy; or targeted therapy, for metastatic RCC.
• Adequate organ function

Exclusion Criteria:

• Prior allogeneic stem cell transplantation
• RCC with histology other than clear cell type
• History or presence of brain metastasis