Stereotactic Body Radiation Therapy and T-Cell Infusion in Treating Patients With Metastatic Kidney Cancer

PRIMARY OBJECTIVES:

I. Conduct a safety and feasibility study of stereotactic radiotherapy with autologous
T-cell infusion for patients with metastatic renal cell carcinoma.

SECONDARY OBJECTIVES:

I. Determine the progression free survival at one year. II. Determine the overall survival
at one year.

OUTLINE:

STEREOTACTIC BODY RADIATION THERAPY (SBRT): Patients undergo standard of care SBRT over 1-2
weeks according to tumor volume and location.

LYMPHODEPLETION: Beginning 3 weeks later, patients receive cyclophosphamide orally (PO)
twice daily (BID) for 3 days.

REINFUSION OF PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC): Within 3-14 days of completing
lymphodepletion with cyclophosphamide, patients undergo autologous PBMC infusion.

After completion of study treatment, patients are followed up at 1 week, 4 weeks, and
monthly thereafter.

Inclusion Criteria:

- Histologically confirmed carcinoma of the kidney (clear-cell predominance)

- Have had at least 2 prior systemic treatments for renal cell carcinoma (RCC)

- Have at least 1 extracranial metastasis that is amenable to radiation and at least 1
other site of disease that is measurable by Response Evaluation Criteria in Solid
Tumors (RECIST)

- Subjects must provide written informed consent prior to performance of study-specific
procedures or assessments, and must be willing to comply with treatment and follow up

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2

- Absolute neutrophil count (ANC) >= 0.75 x 10^9/L

- Absolute lymphocyte count (ALC) >= 0.5 X 10^9/L

- Hemoglobin >= 8 g/dL

- Platelets >= 50 X 10^9/L

- Total bilirubin =< 3 X upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 X ULN

- Serum creatinine =< 2.1 X ULN (or creatinine clearance of > 50 cc/min)

Exclusion Criteria:

- History of other malignancies within 5 years prior to enrollment except for tumors
with a negligible risk for metastasis or death, such as adequately controlled basal
cell carcinoma, squamous-cell carcinoma of the skin, carcinoma in situ of the cervix,
early-stage bladder cancer, or low-grade endometrial cancer

- Malignancies that have undergone a putative surgical cure (i.e., localized
prostate cancer post-prostatectomy) within 5 years prior to enrollment may be
discussed with the lead primary investigator

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or
anti-seizure medication for more than 1 week within 6 months prior enrollment

- Presence of uncontrolled infection

- Evidence of active bleeding or bleeding diathesis; any medical condition requiring
systemic anticoagulation (including anti-platelet agents)

- Any serious and/or unstable pre-existing medical, psychiatric, or other condition
that could interfere with subject's safety, provision of informed consent, or
compliance to procedures

- Pregnant and breastfeeding women are excluded; as well as women of child-bearing
potential who are unwilling or unable to use an acceptable method of birth control
(hormonal or barrier method of birth control; abstinence) to avoid pregnancy for the
duration of the study