P1101 in Treating Patients With Myelofibrosis

Study Overview
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Brief Summary
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This pilot phase II trial studies P1101 (polyethyleneglycol [PEG]-proline-interferon alpha-2b) in treating patients with myelofibrosis. PEG-proline-interferon alpha-2b is a substance that can improve the body's natural response and may slow the growth of myelofibrosis.

Detailed Description
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PRIMARY OBJECTIVE: 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). EXPLORATORY AND CORRELATIVE RESEARCH 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.

Official Title
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Phase II Study of P1101 in Early Myelofibrosis

Conditions
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Primary Myelofibrosis, Secondary Myelofibrosis

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Other: Quality-of-Life Assessment
* Biological: Ropeginterferon Alfa-2B


Participation Criteria
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Eligibility Criteria
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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 (obtained =< 14 days prior to registration) Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration) Aspartate transaminase (AST) =< 2.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration) Alanine aminotransferase (ALT) =< 2.5 x ULN (obtained =< 14 days prior to registration) Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (PEG-proline-interferon alpha-2b)<br>Patients receive PEG-proline-interferon alpha-2b SC on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Biological: Ropeginterferon Alfa-2B<br>* Given SC<br>* Other names: PEG-Proline-Interferon Alfa-2b;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response (CR, PR, or CI) as determined by International Working Group Criteria | The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time | The distribution of survival time will be estimated using the method of Kaplan-Meier. | Time from registration to death due to any cause, assessed up to 3 years | 
| Incidence of adverse events, as measured by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4) | The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. | Up to 3 years |