Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine the proportion of patients with chronic neutrophilic leukemia (CNL) and
atypical chronic myeloid leukemia (aCML) who have a hematologic response to ruxolitinib
(ruxolitinib phosphate) (partial response [PR], complete response [CR], complete response,
partial [CRp]).

SECONDARY OBJECTIVES:

I. To determine the frequency of grade 3 or 4 hematologic and non-hematologic adverse events
experienced by subjects during therapy with ruxolitinib.

II. To determine whether hematologic responses correlate with certain types of mutations in
colony stimulating factor 3 receptor (CSF3R) and reduction in mutant CSF3R allele burden in
the peripheral blood.

III. To determine the maximum clinical responses for each subject and the median duration of
maximum clinical responses.

IV. To determine the mean % reduction of spleen size, estimated by volume using the
conventional prolate ellipsoid method as measured by ultrasound compare to baseline.

V. To determine the mean % reduction of total symptom score as measured by a modified
Myeloproliferative Neoplasm Symptom Assessment Form version 2.0 (MPN-SAF) compared to start
of study (day 1, cycle 1).

VI. To determine overall survival in subjects who complete a minimum of 1 dose of study drug.

VII. To determine the proportion of subjects who discontinue after completion of > 3 cycles
but < 6 cycles.

VIII. To determine the proportion of subjects who discontinue prior to completion of cycle 3.

OUTLINE:

Patients receive ruxolitinib phosphate orally (PO) every other day, once daily (QD), or twice
daily (BID) on days 1-28. Each patient will be followed for a maximum of 96 weeks (24 cycles,
1 cycle is 4 weeks long). If the study drug continues to be effective, the patient may be
eligible to continue on study drug past 24 cycles.

After completion of study treatment, patients are followed up within 2 weeks and at 4-6
weeks.

Inclusion Criteria:

- Subjects must be newly diagnosed or previously diagnosed with CNL or aCML; all
patients must have a bone marrow biopsy completed during the screening or baseline
period if one has not been done within 90 days of day 1, cycle one

- Subjects must have platelet count greater than 25,000 per microliter at baseline and
at the start of study (day 1, cycle 1) visit

- Subjects must be able to discontinue any drug treatment aimed at lowering disease
burden in CNL or aCML; subjects should discontinue hydroxyurea to treat underlying CNL
or aCML disease no later than day -7 (one week before starting ruxolitinib); for drugs
that have more long-lasting effects on the marrow, such as thalidomide and its
analogs, and interferon, subjects should discontinue these no later than day -28

- Subjects must be willing to accept/continue transfusions to treat low hemoglobin
levels

- Subjects must have a life expectancy of > 6 months

Exclusion Criteria:

- Subjects unable to review and sign informed consent form

- Females who are pregnant or breastfeeding, and males and females who cannot comply
with requirements to avoid fathering a child or becoming pregnant

- Subjects with known diagnosis of human immunodeficiency virus (HIV) or chronic active
Hepatitis B or C; viral testing is not required; subjects with a history of Hepatitis
B and/or C are allowed on trial if the virus is undetected at the time of enrollment

- Subjects with inadequate liver (alanine aminotransferase [ALT]/serum glutamate
pyruvate transaminase [SGPT] above 4 X upper limit of normal [ULN] or direct bilirubin
4 X ULN AND the lab abnormalities are felt to be due to underlying liver dysfunction)

- Subjects with end stage renal function (creatinine clearance [CrCl] < 15 mL/min or
glomerular filtration rate [GFR] <15 mL/min) regardless of whether hemodialysis is
required

- Subjects with clinically serious infections requiring ongoing antibiotic therapy

- Subjects with severe (immediately life threatening) and recent (occurring within the
last 3 months) cardiac dysfunction, pulmonary dysfunction, esophageal variceal
bleeding, hemorrhagic strokes, or intracranial hemorrhage are not eligible for study
participation

- Subjects requiring therapeutic doses of anticoagulation or anti-platelet therapies
(aspirin above 81 mg daily, Plavix or similar agents) AND platelet counts are below
50,000 on two different laboratory evaluations, separated by minimum of two weeks

- Taking investigational or commercial agents or therapies with the intent to treat the
subject's malignancy other than those therapies permitted

- Subjects with invasive malignancy over the previous 2 years except treated early stage
carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix,
and completely resected papillary thyroid and follicular thyroid cancers

- Previous allergic reactions to janus kinase (JAK) inhibitors or excipients

- Prior therapy with ruxolitinib or other JAK inhibitors

- Subjects who have had major surgery within 4 weeks prior to entering the study

- Subjects who are anticipated to receive a transplant within the first 6 months of
treatment on trial