Ruxolitinib Phosphate in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell or Peripheral T-Cell Non-Hodgkin Lymphoma After Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. Assess the overall response rate (ORR) of subjects with relapsed diffuse large B-cell
lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL) who are relapsed or refractory to
front-line treatment and ineligible for stem cell transplantation or have recurrent disease
after stem cell transplantation to oral ruxolitinib (ruxolitinib phosphate).

SECONDARY OBJECTIVES:

I. Evaluate safety of oral ruxolitinib in subjects with DLBCL and PTCL. II. Determine
progression-free survival (PFS), duration of response, and overall response (OS) in subjects
with DLBCL and PTCL.

TERTIARY OBJECTIVES:

I. Explore the relationship between responses to oral ruxolitinib and alterations in gene
expression profiling (GEP) signatures as well as biomarker immunophenotypic changes related
to JAK2/STAT3, NF-kB, PI3K/AKT, and mTOR pathways.

II. Evaluate potential effect of oral ruxolitinib exposure on JAK2/STAT3 pathway inhibition
in serial tumor samples.

OUTLINE:

Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months thereafter.

Inclusion Criteria:

- Subjects must have histologically documented relapsed or refractory disease, with a
diagnosis of one of the following lymphoid malignancies: diffuse large B-cell
lymphoma, peripheral T-cell lymphoma (any subtype); subjects must have received at
least one prior systemic chemotherapy and must have either received an autologous stem
cell transplant, refused or been deemed ineligible for an autologous stem cell
transplant

- Subjects must be willing and able to have a fresh tumor biopsy prior to start of study
treatment for research evaluations and cohort categorizing; Note: if insufficient
fresh tissue is obtained to provide sub-classification for cohorts, then tissue
material from a previous relapse biopsy and/or original diagnostic block may be
requested to meet this criterion

- Subjects must have measurable lesions (at least one target lesion measuring 2 cm in
diameter) by computerized tomography (CT) scan, and/or measurable lymphoma cutaneous
lesions of any size

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Absolute neutrophil count (ANC) >= 1,000/mm^3

- Platelet count >= 75,000/mm^3

- Hemoglobin >= 8.0 g/dL

- Serum creatinine =< 2.0 g/dL or calculated creatinine clearance >= 60 mL/min
(Cockcroft-Gault method)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x
institutional upper limit of normal (ULN) or =< 5 x ULN if liver involved by lymphoma

- Bilirubin < 2.0 x ULN unless subject has Gilbert's disease, low-grade hemolysis, or
liver involvement with lymphoma

- At least 2 weeks since prior chemotherapy, biological therapy, radiation therapy,
major surgery, other investigational, or anti-cancer therapy that is considered
disease-directed and recovered from prior toxicities to grade 0-1 at least 2 weeks
prior to investigational therapy

- Females will be either postmenopausal for at least 1 year or surgically sterile for at
least 3 months; OR females of child-bearing potential must have a negative pregnancy
test at screening and agree to take appropriate precautions to avoid pregnancy from
screening until 3 months after their last dose of study medication

- Males must agree to take appropriate precautions to avoid fathering a child from
screening until 3 months after their last dose of study medication

- Able to comprehend and willing to sign an informed consent form (ICF)

Exclusion Criteria:

- History of or active central nervous system (CNS) malignancy

- Allogeneic stem cell transplant within the last 6 months, or active-graft-versus-host
disease following allogeneic transplant, or subjects currently on immunosuppressive
therapy following allogeneic transplant

- Uncontrolled intercurrent illness including, but not limited to, ongoing active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situation that would limit compliance with
study requirements as judged by treating physician; subjects receiving antibiotics
that are under control may be included in the study

- Pregnant or breastfeeding women

- Clinically symptomatic and uncontrolled cardiovascular disease

- History of myocardial infarction, severe/unstable angina, or symptomatic congestive
heart failure, within the 6 months prior to study drug administration

- Current or recent history (< 21 days prior to start of treatment) of a clinically
significant bacterial, viral, fungal, parasitic or mycobacterial infection

- History of other malignancy, with the exception of squamous cell carcinoma of the
skin, basal cell carcinoma of the skin, cervical intraepithelial neoplasia, or other
malignancies that have been in remission for at least 3 years

- Presence of a malabsorption syndrome possibly affecting drug absorption (e.g., Crohn's
disease or chronic pancreatitis)

- Any prior or concomitant use of another JAK inhibitor

- Known active hepatitis B or C, or human immunodeficiency virus (HIV) infection

- Subjects who, in the opinion of the investigator, are unable or unlikely to comply
with the dosing schedule and study evaluations