Pyrimethamine in Treating Patients with Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or T-Cell Large Granular Lymphocyte Leukemia

Inclusion Criteria

• Subjects must be diagnosed with CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma) based on the standard histologic and immunophenotypic criteria described in the World Health Organization (WHO) classification of lymphoid malignancies, including immunophenotypic confirmation that the tumor cells co-express B cell antigens cluster of differentiation (CD)19/20 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 (Dana-Farber Cancer Institute [DFCI], Brigham and Women's Hospital [BWH], Massachusetts General Hospital [MGH], Beth Israel Deaconess Medical Center [BIDMC]) within approximately one month after the subject is registered; any question on histology confirmation should be brought to the attention of the Principal Investigator
• Participants must have measurable disease, defined as lymphocytosis >= 5,000/ul, or at least one palpable or CT measurable lesion > approximately 1.5 cm, or bone marrow involvement > approximately 30%
• Subjects must have relapsed after at least one prior purine analogue-containing regimen (fludarabine, cladribine or pentostatin), OR at least two non-purine analogue containing regimens
• T-LGL judged by the investigator to require therapy based upon: *Severe neutropenia (absolute neutrophil count < 500/microL) *Moderate neutropenia (absolute neutrophil count < 1000/microL) with recurrent infections *Symptomatic or transfusion dependent anemia *Severe thrombocytopenia (< 50,000/microL) *Hepatic infiltration resulting in abnormal liver function tests *Symptomatic splenomegaly
• Patients with previously untreated or relapsed/refractory disease will be eligible
• Life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Karnofsky >= 60%
• Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) unless due to indirect hyperbilirubinemia related to Gilbert's syndrome or hemolysis, or to disease infiltration
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X institutional upper limit of normal
• Creatinine =< 2 X institutional ULN
• Subjects must require treatment based on International Workshop on CLL (IWCLL) 2008 criteria
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Participants who have had 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; the Principal Investigator or treating investigator determine if any abnormal laboratory values or toxicities are due to prior agents administered vs. disease and if they are clinically significant
• Participants may not be receiving any other study agents
• Known central nervous system (CNS) involvement with CLL or T-LGL
• 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 stem cell transplantation (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 (the latter is permitted)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection not controlled by appropriate antibacterial, antiviral or antifungal therapy, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with pyrimethamine
• Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy are ineligible