P1101 in Treating Patients With Myelofibrosis

PRIMARY OBJECTIVES:

I. To evaluate for clinical response (complete remission [CR], partial remission [PR], or
clinical improvement [CI]) as defined by International Working Group-Myeloproliferative
Neoplasms Research and Treatment (IWG-MRT) criteria in a cohort of intermediate-2/high risk
myelofibrosis (MF) patients. Response in a second cohort of early stage MF patients will also
be described.

SECONDARY OBJECTIVES:

I. To evaluate the adverse event profile of P1101 in patients with myelofibrosis by cohort
(early vs intermediate-2/high risk).

II. To evaluate the tolerability of P1101 in patients with myelofibrosis by cohort (early vs
intermediate-2/high risk).

TERTIARY OBJECTIVES:

I. To evaluate quality of life (QOL) and patient-reported symptoms using the
Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) with P1101 for patients with
myelofibrosis by cohort (early vs intermediate-2/high risk).

II. To evaluate the impact of P1101 on bone marrow and histological features of myelofibrosis
including cytogenetics, blast percentage, fibrosis, and JAK2-V617F allele burden by cohort
(early vs intermediate-2/high risk).

OUTLINE:

Patients receive PEG-proline-interferon alpha-2b subcutaneously (SC) on days 1 and 15.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 3 years.

Inclusion Criteria:

- Evaluable myelofibrosis by IWG-MRT criteria including one or more of the following:

- Spleen >= 5 cm below the left costal margin

- MPN-SAF total symptom score (TSS) > 10 at baseline

- Hemoglobin < 10 g/dL

- Confirmed diagnosis of myelofibrosis (primary myelofibrosis or myelofibrosis secondary
to essential thrombocythemia or polycythemia vera) by World Health Organization (WHO)
diagnostic criteria (3 major and 2 minor criteria: major criteria: megakaryocyte
proliferation and atypia with either reticulin and/or collagen fibrosis, not meeting
criteria for chronic myelogenous leukemia [CML], polycythemia vera [PV],
myelodysplastic syndrome [MDS], or other myeloid neoplasm, JAK2V617F or other clonal
marker or no evidence of reactive marrow fibrosis; minor criteria:
leukoerythroblastosis, increased lactate dehydrogenase [LDH], anemia, palpable
splenomegaly)

- For cohort 1: early stage MF (low or intermediate 1 stage as defined by Dynamic
International Prognostic Scoring System [DIPSS]) without currently available treatment
options

- For cohort 2: intermediate-2 or high risk MF patients as defined by DIPSS either not
eligible for ruxolitinib or having failed under ruxolitinib

- No prior treatment for myelofibrosis (for cohort 1 only)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- Platelet count >= 100,000/mm^3

- Absolute neutrophil count (ANC) >= 1000/mm^3

- Aspartate transaminase (AST) =< 2.5 x upper limit of normal (ULN)

- Alanine aminotransferase (ALT) =< 2.5 x ULN

- Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault formula

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- Ability to complete questionnaire(s) by themselves or with assistance

- Provide informed written consent

- Willing to return to enrolling institution for follow-up

- Willing to provide blood samples for correlative research purposes

Exclusion Criteria:

- Patients who have had chemotherapy or radiation =< 2 weeks of registration

- For cohort 1 only: patients with evidence of intermediate 2 or high risk disease
(according to DIPSS)

- For cohort 1 only: patients with a bone marrow biopsy with < 15% cellularity, evidence
of collagen fibrosis, osteosclerosis, or blasts > 10% in peripheral blood or marrow
(demonstrating advanced disease)

- Patients who have received a prior stem cell transplant

- Patients who have received radiation to the spleen within 3 months prior to
registration

- Patients with intolerance to compounds similar to pegylated interferon alpha-2b

- Patients with evidence of >= grade 2 peripheral sensory neuropathy

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Immunocompromised patients or patients known to be human immunodeficiency virus (HIV)
positive and currently receiving antiretroviral therapy

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

- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm

- History of myocardial infarction =< 6 months prior to registration, or congestive
heart failure requiring use of ongoing maintenance therapy for life-threatening
ventricular arrhythmias

- History of significant or major funduscopic findings including, but not limited to,
retinal exudates, hemorrhage, detachment, neovascularization, papilledema, optic
atrophy, micro-aneurysm or macular changes

- Other active malignancy at time of registration; EXCEPTIONS: non-melanotic skin cancer
or carcinoma-in-situ of the cervix