Pegylated Interferon Alfa-2a Salvage Therapy in High Risk Polycythemia Vera (PV) or 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:

    II 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: 12-002751
  • NCT ID:

    NCT01259817
  • Sponsor Protocol Number:

    MPD-RC 111

About this study

The aim of this research is to look 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.

It is important for patients with ET or PV who are at risk of blood clots to receive drugs which will minimize the risks of developing these blood clots but at the moment the investigators are not sure which drugs will best control the disorder.

The purpose of this study is to look at the effectiveness of giving patients who have been diagnosed with ET and PV a study drug regimen using Aspirin and PEGASYS (also known as Pegylated interferon alfa-2a, instead of the standard treatment drug called Hydroxyurea (or hydroxycarbamide or Hydroxyurea), for whom this drug may not be suitable. The drug may not be suitable either because it is not adequately controlling the number of blood cells or some specific side effects occur.

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 ET or PV shall be made in accordance with the WHO (2008) criteria (Swerdlow 2008) as shown below (Values below are at the time of diagnosis, not study 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 or little granulocyte or erythroid proliferation. Patients may have up to and including 2+ marrow reticulin fibrosis.
      3. Not meeting WHO criteria for CML, PV, MDS, PMF or over myeloid neoplasm
      4. Demonstration of clonal cytogenetic marker or no evidence for a 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 (i.e. > 5cm below costal margin on palpation) 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 (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
  • In addition patients must EITHER be intolerant or resistant to Hydroxyurea according to established criteria as follows:
    • Any ONE of the following:
      • Platelet count > 600 x 10 to 9/L after 3 months of at least 2 g/day of Hydroxyurea (2.5 g/day in patients with a body weight>80 kg)
      • Platelet count > 400 x 10 to 9/L and WBC less than 2.5 x 10 to 9/L at any dose of Hydroxyurea (for a period of at least 2 months). Platelet count > 400 x 10 to 9/L and Hb less than10 g/dl at any dose of Hydroxyurea (for a period of at least 2 months) Progressive splenomegaly or hepatomegaly (>5cm or appearance of new splenomegaly or hepatomegaly) in a patient being treated for splenomegaly In patients with baseline splenomegaly an increase by > 5 cm over baseline
      • Not achieving the desired reduction of HCT with the addition of Hydroxyurea in patients who do not tolerate enough frequent venesections after 3 months of at least 2 g/day of Hydroxyurea (2.5 g/day in patients with a body weight>80 kg)
      • Not achieving the desired stable reduction of WBC when leukocytes are a target of therapy after 3 months of at least 2 g/day of Hydroxyurea (2.5 g/day in patients with a body weight > 80 kg)
      • Presence of leg ulcers or other unacceptable Hydroxyurea-related non-hematological toxicities, such as unacceptable mucocutaneous manifestations, gastrointestinal symptoms, pneumonitis or fever at any dose of Hydroxyurea.
  • OR have Splanchnic Vein Thrombosis (SVT) (includes Budd-Chiari, abdominal vein thrombosis, portal vein thrombosis, splenic vein thrombosis). For these patients the following additional inclusion/exclusion criteria apply:
    • > 3 months since onset of SVT
    • SVT treated with oral anticoagulants but no aspirin
    • Liver enzymes not > 2 times the normal value
    • Absence of encephalopathy, refractory or infected ascites, esophageal varicose of grade > 1 at time of trial entry
    • Bone marrow biopsy confirmed diagnosis of PV or ET
    • JAK2-V617F mutations present
    • These patients may have a normal blood count at trial entry
  • Age over 18 years (no upper age limit)
  • Able and willing to comply with study criteria
  • Signed and informed consent to participant in this study
  • Willing to participate in associated correlative science biomarker study
  • Serum creatinine < 1.5 x upper limit of normal
  • AST and ALT < 2 x upper limit of normal
  • Total bilirubin within normal limits

Exclusion Criteria:

  • Patients cannot have any other form of chemotherapy for their MPD (other than hydroxyurea). Specifically prior interferon or JAK2 inhibitors are prohibited.
  • If a patient has received prior hydroxyurea, they should be tapered off hydroxyurea over a period of the first 2 months of Pegylated interferon alfa-2a therapy. Taper is at the treating physician's discretion, but must be absent (completed) by the start of the third month.
  • Presence of any life-threatening co-morbidity
  • History of active substance or alcohol abuse within the last year
  • Any contraindications to pegylated or non-pegylated interferon
  • Subjects who have a positive pregnancy test, are pregnant, lactating or of reproductive potential and not practicing an effective means of contraception
  • History of psychiatric disorder (e.g. depression; suicidal ideation; psychosis)
  • History of autoimmune disorder (e.g. hepatitis; ITP; scleroderma; severe psoriasis affecting > 10% of the body, rheumatoid arthritis requiring more than intermittent NSAID for management)
  • Hypersensitivity to IFN-α
  • 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
  • Any investigational drug < 6 weeks prior to the first dose of study drug or not recovered from effects of prior investigational agent.
  • Presence of JAK2 exon 12 mutation
  • Patients should not meet criteria for post PV or post ET-MF
  • No previous exposure to any formulation of interferon
  • 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.
  • History of major organ transplantation
  • History of uncontrolled severe seizure disorder
  • Inability to give informed written consent
  • Serum creatinine > 1.5 x upper limit of normal
  • AST and ALT > 2 x upper limit of normal
  • Total bilirubin > 1.5 mg/ml
  • No detectable PNH (paroxysmal nocturnal hemoglobinuria) clone where tested
  • Concurrent hormonal contraceptive use

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