Pegylated Interferon Alpha-2b in Early Primary Myelofibrosis

Subjects will be randomized into one of the study groups: one in which subjects get treated
with PEGINTRON and the other in which subjects are closely followed and get best supportive
care until disease progression (the presently accepted standard approach for early disease).
Subjects on the observation arm will be carefully monitored for clinical or laboratory
progression of disease during scheduled study visits. However, they will not be treated with
an active drug like Interferon alfa or others such as Hydroxyurea, Revlimid, Thalidomide,
Pomalidomide, and the newly approved JAK2 (Janus Kinase 2) inhibitor Ruxolitinib (Jakafi). If
their disease progresses, they will be eligible for cross-over into the treatment arm with
PEGINTRON. Subjects randomized to the treatment arm will receive PEGINTRON once weekly.

Inclusion Criteria:

- Patients must meet laboratory, and bone marrow histological criteria for primary
myelofibrosis as defined by World Health Organization (WHO) diagnostic criteria as follows:

WHO diagnostic criteria for PMF Proposed Criteria for PMF Major Criteria

1. Presence of megakaryocyte proliferation and atypia, usually accompanied by either
reticulin and/or collagen fibrosis, or, in the absence of significant reticulin
fibrosis, the megakaryocyte changes must be accompanied by an increased bone marrow
cellularity characterized by granulocytic proliferation and often decreased
erythropoiesis (ie. prefibrotic cellular-phase disease)

2. Not meeting WHO criteria for Polycythemia Vera (PV), Chronic Myeloid Leukemia (CML),
Myledysplastic Syndrome (MDS), or other myeloid neoplasm

3. Demonstration of JAK2617V>F or other clonal marker (e.g. MPL515W>L/K), or in the
absence of a clonal marker, no evidence of bone marrow fibrosis due to underlying
inflammatory or other neoplastic disease

Minor Criteria

1. Leukoerythroblastosis

2. increase in serum Lactase Dehydrogenase (LDH)

3. Anemia

4. Palpable splenomegaly

- Patients must have Low or Intermediate 1 stage of disease as defined by
International Working Group (IWG) risk stratification of primary myelofibrosis in
the dynamic international prognostic scoring system (DIPSS). In addition, they
must show some active hematopoiesis with a cellularity of at least 15%,
irrespective of the degree of reticulin and/or collagen fibrosis as defined by
Manoharan criteria.

- Patients should NOT have had prior therapy for primary myelofibrosis. This
includes treatment with cytoreductive drugs (Hydroxyurea), immunomodulatory drugs
(thalidomide, lenalidomide, pomalidomide), JAK2 inhibitors, or other therapies
specifically for myelofibrosis. If they received these classes of drugs for
indications other than PMF, treatment should be discontinued at least 6 weeks
prior to randomization.

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

- Patients must have normal organ and marrow function as defined below:

- White blood cell (WBC) ≥ 3,000/microL

- Absolute Neutrophil Count (ANC) ≥ 1,500/microL

- Platelets ≥ 100,000//microL

- Total bilirubin within normal limits

- Aspartate aminotransferase - serum glutamic oxaloacetic transaminase
(AST(SGOT)) and alanine aminotransferase - serum glutamic pyruvic
transaminase (ALT(SGPT)) less than or equal to 2.5 X upper limit of normal

- Creatinine Clearance ≥ 50 ml/min

- The effects of peg-IFNα-2b on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason, women of child-bearing potential
and men must agree to use adequate contraception (hormonal or barrier method of
birth control; abstinence) prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician
immediately.

- Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria

- Patients who have had chemotherapy or radiotherapy within 6 weeks prior to entering
the study or those who have not recovered from adverse events due to agents
administered more than 6 weeks earlier.

- Patients with Intermediate 2 or High risk stage of disease as defined by International
Working Group (IWG) risk stratification of primary myelofibrosis in the dynamic
international prognostic scoring system (DIPSS) and/or bone marrow biopsy showing less
than 15% cellularity in the presence +2 or more reticulin fibrosis (by Manoharan
criteria), collagen fibrosis, or osteosclerosis.

- Patients may not be receiving any other investigational agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to peg-IFNα-2b

- Other Exclusion Criteria

- Female patients who are pregnant or breast feeding

- History of depression or active treatment for depression

- History of non-compliance to medical regimens

- History of autoimmune diseases

- History of hypothyroidism or hyperthyroidism

- Clinical evidence of neuropathy

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

- Pregnant and lactating women are excluded from the study because the risks to an
unborn fetus or potential risks in nursing infants are unknown.