Study of Ruxolitinib in Relapsed or Refractory T or NK Cell Lymphoma

Inclusion Criteria:

• Pathologically confirmed T or NK cell lymphoma at the enrolling institution. ForCTCL, 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 ormorphology 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 beendiscontinued at least 2 weeks prior to treatment.

• Glucocorticoids aimed at controlling lymphoma-related symptoms are allowed aslong as they are tapered down to 20mg or less by the time of ruxolitiibinitiation

• Topical steroids for CTCL are permitted

• See section 6.2 Subject Exclusion Criteria for guideline regarding adjuvant andmaintenance 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 tolymphoma), 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 hemoglobinvalue for eligibility

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or; ≤ 3 x ULN if documentedhepatic involvement with lymphoma, or ≤ 5 x ULN if history of Gilbert's ; ASTand 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 beallowed as long as baseline platelets are ≥ 150 x 10^9/L

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

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

Exclusion Criteria:

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

• Uncontrolled concurrent illness including, but not limited to, ongoing or activeinfection, uncontrolled diabetes, clinically significant pneumonitis, symptomaticcongestive heart failure, unstable angina pectoris, cardiac arrhythmia, orpsychiatric illness/social situations that would limit compliance with studyrequirements.

• ECOG performance status >2

• Prior therapy with ruxolitinib

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

• Patients with more than one type of lymphoma may be enrolled after discussionwith the MSK Principal Investigator

• Adjuvant or maintenance therapy to reduce the risk of recurrence of othermalignancy (other than T-cell lymphoma) is permissible after discussion withthe MSK principal Investigator

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

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