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: LGL cell population meeting diagnostic criteria (defined as CD3+CD8+ cell population > 650/mm3 or CD3+CD8+CD57+ population > 500/mm3 or LGL cell population with other immunophenotype that includes co-expression of CD3+, CD8+, CD57+ with > 500 cells/mm3 and the presence of a clonal T-cell receptor [within 1 month of diagnosis or relapse]). This also includes patients with rare T-LGLL variants include CD4+ T-LGLL, and gamma/delta T-LGLL which can be CD4- and CD8-), though patients still must have the presence of a clonal T-cell receptor within 1 month of diagnosis or relapse * Note: Since many pre-treated patients with T-LGLL do not have high T-LGLL cell counts, but have active disease, patients with T-LGLL may be included with principal investigator (PI) approval even if CD3+CD8+ cell population is < 650/mm3 or CD3+CD8+CD57+ population is < 500/mm3, though +TCR is required. Natural-Killer (NK) LGL is also permitted, provided there is a clonal NK-cell population noted with > 500 cells/mm3
• Failed at least one line of frontline therapy
• 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 10^9/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]). (For example: If a patient has an eGFR of 60 mL/min/1.73 m^2 and a body surface area [BSA] of 1.8 m^2, the calculation would be 60 mL/min/1.73 m^2 x (1.8 m2 / 1.73 m^2) which gives eGFR of 62.4 mL/min)
• Total bilirubin ≤ 1.5 x upper limit of normal (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. Note: granulocyte colony-stimulating factor (G-CSF) may be utilized to enable patients to meet inclusion criteria, as long as the ANC remains above 100/mm^3 for 5 days after administration of last growth-factor.
• 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. Patients with tuberculosis risk factors will be required to undergo quantiferon testing and/or purified protein derivative (PPD) testing with a negative result prior to entering the study
• 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 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
• For any strong CYP3A4 inhibitors deemed a moderate or severe risk of interaction with ruxolitinib, a wash-out period of 14 days, or 5 half-lives, whichever is longer, is needed prior to starting ruxolitinib
• Given the CYP3A4 inhibition potential of grapefruit, grapefruit juice, Seville orange juice, pomelos, and starfruits, patients will need to refrain from these foods/drinks for 14 days prior to initiation of therapy, and throughout the study period