Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea in Polycythemia Vera (PV) and Essential Thrombocythemia (ET)

Completed · Phase 3

Conditions studied: High Risk Polycythemia Vera, High Risk Essential Thrombocythemia

In brief

This research is looking at two conditions, Essential Thrombocythemia (ET) and Polycythemia Vera (PV). ET causes people to produce too many blood cells called platelets and PV causes too many platelets and red blood cells to be made. Platelets are particles which circulate in the blood stream and normally prevent bleeding and bruising. Having too many platelets in the blood increases the risk of developing blood clots, which can result in life threatening events like heart attacks and strokes. When the number of red blood cells is increased in PV this will slow the speed of blood flow in the body and increases the risk of developing blood clots. The purpose of this study is to look at the effectiveness of giving participants who have been diagnosed with ET or PV one of two different study regimens over time. The study subject will be followed for their condition for about 5 years. The subject will be randomized into one of two study regimens, either Pegylated Interferon Alfa-2a (PEGASYS) or Aspirin and Hydroxyurea (also called Hydroxycarbamide). The subject must be newly diagnosed or already receiving treatment for either PV or ET. Each of the study drugs used in this study is already being used to treat subjects with ET or PV currently, but the investigators are unsure which study drug is better.

Key facts

Study ID: NCT01259856
Run by: Ronald Hoffman
People needed: 168
Starts: 2011-09-01
Expected to finish: 2017-06-30
Last updated by the study team: 2019-04-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

A diagnosis of Essential Thrombocythemia (ET) or Polycythemia Vera (PV) shall be made in accordance with the WHO (2008)criteria (Swerdlow 2008) as shown below.
Diagnosis < 5 years prior to entry.
Polycythemia Vera (2 major criteria required)
Hb >18.5g/dl (♂) or 16.5g/dl (♀) or HCT >99 percentile reference range or Elevated red cell mass (>25% above mean predicted value) or Hb >17g/dl (♂) or 15g/dl (♀) if associated with a sustained rise from baseline with no apparent cause (e.g. treated iron deficiency).
Presence of JAK2V617F
If source documentation of diagnostic criterion #1 cannot be obtained, then diagnosis can be made with (1) the addition of an erythropoietin level below the reference range of normal AND (2) bone marrow biopsy showing hypercellularity for age with trilineage (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation.
Essential Thrombocythemia (all 6 criteria required)
Platelets count ≥ 450 x 10 to 9/L
Megakaryocyte proliferation with large and mature morphology. No significant increase or left shift of neutrophil granulopoiesis or erythropoiesis. Patients may have up to and including 2+ marrow reticulin fibrosis (0, 1 or 2 on scale 0 -4).
Not meeting WHO criteria for CML, PV, MDS, PMF or other myeloid neoplasm
Demonstration of clonal cytogenetic marker or no evidence of reactive thrombocytosis.
Absence of a leukoerythroblastic blood picture.
May participate in study without presence of JAK2V617F.
Patients must have high risk disease as defined below:
High risk PV ANY ONE of the following:
Age ≥ 60 years
Previous documented thrombosis, erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related
Significant splenomegaly (> 5cm below the left costal margin on palpitation) or symptomatic splenomegaly (splenic infarcts or requiring analgesia)
Platelets ≥ 1000 x 10 to 9/L
Diabetes or hypertension requiring pharmacological therapy for > 6 months
High risk ET ANY ONE of the following:
Age ≥ 60 years
Platelet count ≥ 1500 x 10 to 9/L
Previous documented thrombosis, erythromelalgia or migraine headaches (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related
Previous hemorrhage related to ET

You may not qualify if…

(ANY of the following, both strata)
Known to meet the criteria for primary myelofibrosis (as opposed to ET) by WHO 2008
Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
Any contraindications to pegylated interferon or hydroxyurea
Presence of any life-threatening co-morbidity
History of active substance or alcohol abuse within the last year
Subjects who are pregnant, lactating or of reproductive potential and not practicing an effective means of contraception
History of psychiatric disorder (e.g. depression) Subjects with a history of mild depression may be considered for entry into this study, provided that a pretreatment assessment of the subject's affective status supports that the subject is clinically stable based on the investigator's normal practice for such subject.
History of autoimmune disorder (e.g. hepatitis)
Hypersensitivity to interferon alfa
Hepatitis B or C infection (HBV), or untreated systemic infection
Known HIV disease
Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration) or clinically relevant ophthalmological disorder (e.g. due to diabetes mellitus or hypertension)
History or other evidence of decompensated liver disease
History or other evidence of chronic pulmonary disease associated with functional limitation
Thyroid dysfunction not adequately controlled
Neutrophil count <1.5 x 10 to 9/L
JAK2 exon 12 mutation: PV that lacks the JAK2V617F mutation but is characterized by the exon 12 mutation.
Meets criteria for post PV or post ET-MF
Subjects with any other medical condition, which in the opinion of the investigator would compromise the results of the study by deleterious effects of treatment.
Previous exposure to any formulation of pegylated interferon
History of major organ transplantation
History of uncontrolled severe seizure disorder
Inability to give informed written consent
Total bilirubin >1.5 x ULN (patients that have an isolated indirect bilirubin that causes total bilirubin to be elevated beyond 1.5 x ULN due to documented Gilbert's syndrome or hemolysis may be included). No detectable PNH (paroxysmal nocturnal hemoglobinuria) clone where tested

Where it is running

Mayo Clinic — Scottsdale, Arizona, United States
USC Norris Comprehensive Cancer Center — Los Angeles, California, United States
The Palo Alto Clinic — Palo Alto, California, United States
Stanford University School of Medicine — Stanford, California, United States
Georgetown University Medical Center — Washington D.C., District of Columbia, United States
Emory Hospital — Atlanta, Georgia, United States
John H. Stroger Hospital of Cook County — Chicago, Illinois, United States
University of Illinois at Chicago — Chicago, Illinois, United States
University of Kansas Cancer Center — Westwood, Kansas, United States
Icahn School of Medicine at Mount Sinai — New York, New York, United States
Memorial Sloan-Kettering Cancer Center — New York, New York, United States
Weill Cornell Medical College — New York, New York, United States
Duke University Medical Center — Durham, North Carolina, United States
Wake Forest University Baptist Medical Center — Winston-Salem, North Carolina, United States
Geisinger Cancer Center — Danville, Pennsylvania, United States
University of Utah — Salt Lake City, Utah, United States
Hopitaux de Paris — Paris, France
Ospedale Riuniti de Bergamo — Bergamo, Italy
University Of Florence — Florence, Italy
Ospedale San Maartino Genova — Genova, Italy
San Matteo Hospital — Pavia, Italy
Universita Cattolica del Sacro Cuore — Rome, Italy
Belfast City Hospital — Belfast, Northern Ireland, United Kingdom
Heart of England NHS Foundation Trust — Birmingham, United Kingdom
Guy's and St. Thomas' NHS Foundation Trust — London, United Kingdom

Full record on ClinicalTrials.gov

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