Inclusion Criteria:

- Diagnosed with CLL/SLL based on the standard histologic and immunophenotypic criteria
described in the WHO classification of lymphoid malignancies, including
immunophenotypic confirmation that the tumor cells co-express B cell antigens CD19/20
and CD5. Mantle cell lymphoma should be excluded based on positive staining of the
tumor cells for CD23, or the absence of staining of the tumor cells for cyclin D1 or
the absence of t(11;14). This diagnosis should be confirmed at a Dana-Farber/Harvard
Cancer Center institution within approximately one month after the subject is
registered.

- Measurable disease, defined as lymphocytosis > 5,000/uL, or at least one palpable or
CT measurable lesion > approximately 1.5cm, or bone marrow involvement >
approximately 30%

- Relapsed after at least one prior purine analogue-containing regimen, or at least two
non-purine analogue containing regimens

- 18 years of age or older

- Life expectancy of greater than 3 months

- ECOG performance status of 0, 1 or 2

- Normal organ function as outlined in the protocol

- Require treatment based on IWCLL 2008 criteria

- Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation.

Exclusion Criteria:

- Chemotherapy or radiotherapy within 3 weeks prior to entering the study or those who
have not recovered from clinically significant adverse events due to agents
administered more than 3 weeks earlier.

- May not be receiving any other study agents

- Known CNS involvement with CLL

- History of allergic reactions or sensitivity to pyrimethamine

- Patients taking folic acid are eligible if the folic acid is discontinued prior to
pyrimethamine administration and not taken for the duration of time enrolled on this
study

- Prior allogeneic SCT is an exclusion only if the subject has active graft vs. host
disease or requires immunosuppression other than a constant stable dose of
glucocorticoids

- Uncontrolled intercurrent illness

- Pregnant or breastfeeding women

- HIV-positive individuals on combination antiretroviral therapy