The purpose of this research study is to determine if plerixafor can make CLL/SLL (Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma) cells more sensitive to being killed by rituximab, an anti-cancer drug that is commonly used in treating CLL and SLL. In this study, plerixafor will be added to standard treatment with rituximab. Subjects will be monitored to see how well they tolerate the use of these drugs together and how well they work to treat the leukemia.

The primary objective is to determine the maximum tolerated dose (MTD) of plerixafor when combined with rituximab as treatment for previously treated patients with CLL or SLL.

Inclusion Criteria:

• Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period or be surgically sterile. Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during treatment and for 3 months after the treatment period or be surgically sterile.
• Diagnosis of CLL or SLL, relapsed from at least one prior therapy.
• CLL/SLL cells expressing CD20 documented during screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Life expectancy of at least 12 weeks.
• Serum creatinine ≤2.0 mg/dL.
• Total bilirubin ≤2.0 mg/dL.
• ALT (alanine aminotransferase) and AST (aspartate aminotransaminase) ≤2 times the upper limit of normal (ULN); for patients with liver involvement of CLL/SLL disease, this limit is increased to ≤5 times the ULN.
• At the time of enrollment, patients must be >4 weeks since major surgery, radiotherapy, chemotherapy (>6 weeks for some chemotherapies), immunotherapy, biotherapy/targeted or investigational therapies and recovered from the toxicity of prior treatment to ≤ grade 1.

Exclusion Criteria:

• White Blood Cells (WBC) >250 x 10^9 cells/L.
• Disease refractory to rituximab therapy- defined as a failure to respond to prior rituximab-containing regimen.
• Women who are breastfeeding.
• Active viral hepatitis.
• Active infection or treatment with antimicrobial or antiviral therapy within 1 week of enrollment with the exception of prophylactic therapy.
• History of prior allergic reaction to plerixafor or rituximab.
• Significant lung disease.
• Serious cardiac disease such as a history of sustained ventricular arrhythmia, uncontrolled and serious congestive heart failure (CHF), angina, acute coronary syndrome, or myocardial infarction within 6 months of enrollment or other significant medical or psychosocial conditions that warrants exclusion.