The purpose of this study is to test any good and bad effects of the study drug called ruxolitinib. Ruxolitinib works by blocking a protein called JAK. JAK works along with another protein called STAT and is important for survival of many T or NK-cell lymphomas. By blocking JAK, ruxolitinib may cause T or NK-cell lymphomas to shrink.

Inclusion Criteria:

• Pathologically confirmed T or NK cell lymphoma at the enrolling institution. For CTCL, patients with stage IB disease or greater are eligible.

• Relapse or refractory disease after at least 1 systemic therapy except for T-PLL, LGL, or T-cell Lymphoproliferative diseases with JAK2 fusion.

• Untreated patients may be allowed after discussion with P.I.

• Age ≥ 18

• ECOG ≤ 2

• Measurable disease defined by:

  • Lugano Classification for systemic lymphoma or
  • Atypical and or malignant lymphocytes quantifiable by flow cytometry or morphology in blood or bone marrow or
  • mSWAT > 0 or Sezary count ≥ 1000 cells/μL for CTCL

• Previous systemic anti-cancer therapy for T-cell lymphoma must have been discontinued at least 2 weeks prior to treatment.

  • Glucocorticoids aimed at controlling lymphoma-related symptoms are allowed as long as they are tapered down to 20mg or less by the time of ruxolitiib initiation
  • Topical steroids for CTCL are permitted
  • See section 6.2 Subject Exclusion Criteria for guideline regarding adjuvant and maintenance therapy for prior malignancy

• Patients must meet the following lab criteria:

  • ANC ≥ 1.0/mm^3 or ANC >/= 0.5/mm^3 (if patient has baseline neutropenia due to lymphoma), platelets ≥ 100 x 10^9/L or ≥ 50 x 10^9/L (if related to lymphoma), Hgb ≥ 8g/dL
  • Patients with LGL or T-PLL are not required to meet a minimum ANC or hemoglobin value for eligibility
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or; ≤ 3 x ULN if documented hepatic involvement with lymphoma, or ≤ 5 x ULN if history of Gilbert's ; AST and ALT ≤ 3 x ULN; ≤ 5 x ULN if due to lymphoma involvement
  • Creatinine clearance ≥ 30 mL/min; creatinine clearance of 15-29 mL/min will be allowed as long as baseline platelets are ≥ 150 x 10^9/L

• For patients with positive hepatitis B core antibody or surface antigen, hepatitis B PCR must be negative and prophylaxis with entecavir or equivalent is required.

• Patients with HIV are allowed provided that they are on anti-retroviral treatment with no active infections.

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

• Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, clinically significant pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• ECOG performance status >2

• Prior therapy with ruxolitinib

• Receiving systemic therapy for another primary malignancy (other than T-cell lymphoma)

  • Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator
  • Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy (other than T-cell lymphoma) is permissible after discussion with the MSK principal Investigator

• Women of reproductive potential† must have a negative Serum ß human chorionic gonadotropin (ß-HCG) pregnancy test.

  • A female of reproductive potential is a sexually mature female who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).