Ruxolitinib for Adult T-Cell Leukemia

* INCLUSION CRITERIA:

NOTE: After approval and activation of Amendment D, subjects who have failed this protocol treatment previously at the initial dose level may be eligible for re-enrollment and retreatment if they otherwise meet eligibility criteria.

* Subjects greater than or equal to 18 years old with pathologically confirmed adult T- cell leukemia: smoldering or chronic, or previously treated lymphomatous or acute subtypes with clinically indolent behavior indicated by lack of significant symptoms and treatment free interval of greater than 6 months are eligible for treatment in the dose escalation and expansion cohorts.
* Subjects must have serum antibodies directed to human T-cell lymphotropic virus type 1 (HTLV-1).
* Subjects must have measurable or evaluable disease. Subjects with \> 10% of the peripheral blood mononuclear cells (PBMCs) having the characteristic abnormal (i.e., CD3dim, cluster of differentiation 4 (CD4) plus cluster of differentiation 25 (CD25) plus expressing) fluorescence-activated cell sorting (FACS) profile for circulating adult T-cell leukemia (ATL) cells will be considered to have evaluable disease.
* Subjects must have adequate physiologic parameters:
* Absolute granulocyte count greater than or equal to 500 K/microL, platelet count greater than or equal to 75,000 K/microL and hemoglobin greater than or equal to 10 g/dL.
* Bilirubin and creatinine less than or equal to 1.5 times institutional upper limit of normal (ULN).
* Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) less than or equal to 3.0 times institutional ULN.
* Karnofsky Performance Score greater than or equal to 70% or Eastern Cooperative Oncology Group (ECOG) less than or equal 1.
* Subjects must be able to understand and sign Informed Consent Form.

EXCLUSION CRITERIA:

* Subjects with symptomatic leukemic meningitis, bony or gastrointestinal (GI) tract involvement, serum calcium or lactate dehydrogenase (LDH) \> 1.5 times the upper limit of normal will be excluded. However, subjects that have both ATL and another HTLV-1 associated disease such as tropical spastic paraparesis (human T-cell lymphotropic virus type 1 (HTLV-1) Associated Myelopathy (HAM)/tropical spastic paraparesis (TSP) will be included.
* Subjects with symptomatic leukemic meningitis, bony or GI tract involvement, serum calcium or LDH \> 1.5 X the upper limit of normal will be excluded. However, subjects that have both ATL and another HTLV-1 associated disease such as tropical spastic paraparesis (HAM/TSP) will be included.
* Subjects who have received high doses of systemic corticosteroids for the treatment of their ATL within 4 weeks prior to the start of therapy.
* Subjects who have received any cytotoxic therapy, immunotherapy, antitumor vaccines or monoclonal antibodies in the 4 weeks prior to the start of the study.
* Life expectancy of less than 3 months.
* Documented active bacterial infections, HTLV-II infection, or hepatitis B or C as follows:

  * A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antigen (HBsAb) positive and hepatitis B core antibody (HBcAb) negative), or a fully resolved acute hepatitis B infection is not an exclusion criterion.
  * Subjects with an indolent chronic hepatitis B infection (normal ALT, AST, albumin and no radiographic or biopsy evidence of cirrhosis) may be eligible.
  * Subjects with active hepatitis C are excluded. Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
* Subjects who have untreated human immunodeficiency virus (HIV) are not eligible for this study because by definition they have a defective immune response and are at much higher risk for opportunistic infections due to immune disregulation by both HTLV-1 and HTLVIII (HIV) viruses. Subjects on HIV therapy with undetectable viral loads as measured by HIV RNA quantitative real time PCR may be eligible.
* Inability or refusal to practice effective contraception during therapy. Men and women of childbearing potential must use an effective method of birth control or abstinence during treatment and for 1 week after completion of the treatment.
* Subject has significant and/or uncontrolled cardiac, renal, hepatic or other systemic disorders or significant psychological conditions at baseline visit that in the investigators judgment would jeopardize subject enrollment or compliance with the study procedures.
* Subjects with an absolute requirement for a medication that is a strong inhibitor of Cytochrome P450 3A4 (P450 CYP3A4) are not eligible.