Ruxolitinib for the Treatment of T-Cell Large Granular Lymphocytic Leukemia

Inclusion Criteria

• Age 18 or older and able to swallow pills

• Diagnosis of T-LGLL defined as: CD3+CD8+ cell population > 650/mm^3 or CD3+CD8+CD57+ population > 500/mm^3 and the presence of a clonal T-cell receptor (within 1 month of diagnosis). Note: patients with MDS-like T-LGLL may be included with PI approval even if CD3+CD8+ cell population is < 650/mm^3, though +TCR is required. Natural-Killer (NK) LGL is also permitted, provided there is a clonal NK-cell population noted with > 500 cells/mm^3

• Untreated T-LGLL or failed at least one line of frontline therapy;

• Patients must be off treatment for at least 14 days or 5 half-lives, whichever is longer

• Require Treatment for T-LGLL (one or more required)

  • Symptomatic anemia with hemoglobin < 10 g/dL
  • Transfusion-dependent anemia
  • Neutropenia with absolute neutrophil count (ANC) < 500/mm^3
  • Neutropenia with ANC < 1500/mm^3 with recurrent infections

• Platelet count > 50 x 10^9/L. Platelet transfusion may be utilized to meet inclusion criteria, as long as the platelet count remains >50,000/uL within 5 days of last transfusion. Note: Patients with platelets <100 x 109/L and renal impairment are not permitted to enroll to the study. Renal impairment is defined as creatinine clearance (CrCl) < 90 mL/min.

• Serum creatinine =< 2 x the upper limit of normal (ULN)

• • Estimated glomerular filtration rate (eGFR) => 30 mL/min using the Modification of Diet in Renal Disease (MDRD) equation (multiplying eGFR by each subjects Body Surface Area [BSA])

• Total bilirubin =< 1.5 x ULN (patients with Gilbert's syndrome with a bilirubin > 1.5 x ULN permitted)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

• Alkaline phosphatase (ALP) =< 2.5 x ULN

• Eastern cooperative oncology group (ECOG) performance status =< 2

• Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study treatment until 5 half-lives have passed. Male subject agrees to use an acceptable method for contraception for the duration of the study treatment until 5 half-lives have passed.

• Able to sign informed consent

Exclusion Criteria

• Absolute neutrophil count (ANC) less than 100/mm^3
• Active infection requiring ongoing anti-microbial treatment. Patients with human immunodeficiency virus (HIV), positive hepatitis B surface antigen or hepatitis C antibody will be excluded
• Concurrent immune-suppressive therapy (prednisone or equivalent up to 20 mg permitted to treat T-LGL symptoms, but must be weaned within one month of initiation of trial drug). Patients on stable, chronic prednisone =< 10 mg for rheumatologic/autoimmune conditions are exempted from this requirement. They may enroll on the study
• Active, concurrent malignancy unless deemed related to T-LGLL by principal investigator (PI). Early stage skin cancers, prostate cancer, permitted if under no active therapy
• For females of childbearing potential: Positive pregnancy test or lactating
• Unstable angina or myocardial infarction within the past 2 months
• Chronic obstructive pulmonary disease or other interstitial lung disease in active exacerbation
• Cirrhosis