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

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    III What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Scottsdale/Phoenix, Arizona: 11-006934
  • NCT ID:

    NCT01259856
  • Sponsor Protocol Number:

    MPD-RC 112

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • 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 < 3 years prior to entry.
  • Polycythemia Vera (2 major criteria required)
    1. 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).
    2. Presence of JAK2V617F
  • Essential Thrombocythemia (all 6 criteria required)
    1. Platelets count ≥ 450 x 10 to 9/L
    2. 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).
    3. Not meeting WHO criteria for CML, PV, MDS, PMF or other myeloid neoplasm
    4. Demonstration of clonal cytogenetic marker or no evidence of reactive thrombocytosis.
    5. Absence of a leukoerythroblastic blood picture.
    6. 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
      • Diabetes or hypertension requiring pharmacological therapy for > 6 months

      Other Inclusion criteria (Both Strata)

      • Diagnosed less than 3 years prior to entry on trial
      • Never treated with cytoreductive drugs except hydroxyurea for up to 3 months maximum (phlebotomy, aspirin allowed, anagrelide allowed)
      • Age: ≥ 18 years (no upper limit)
      • Ability and willingness to comply with all study requirements
      • Signed informed consent to participate in this study.
      • Willing to participate in associated correlative science biomarker study
      • Serum creatinine ≤ 1.5 x upper limit of normal
      • ST and ALT ≤ 2 x upper limit of normal
      • No known PNH (paroxysmal nocturnal hemoglobinuria) clone
      • No concurrent hormonal oral contraceptive use

Exclusion Criteria: (ANY of the following, both strata)

  • Known to meet the criteria for primary myelofibrosis (as opposed to ET) by WHO 2008
  • 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
  • Splanchnic vein thrombosis (includes Budd-Chiari, portal vein, splenic and mesenteric thrombosis)
  • 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.
  • Patients cannot meet 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.
  • No 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

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Ruben Mesa, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015