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

Completed · Phase 2

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

In brief

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.

Key facts

Study ID

NCT01259817

Run by

Ronald Hoffman

People needed

135

Starts

2011-09-01

Expected to finish

2016-12-01

Last updated by the study team

2017-01-11

Who can join

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

You may qualify if…

• 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)
• 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 or little granulocyte or erythroid proliferation. Patients may have up to and including 2+ marrow reticulin fibrosis.
• Not meeting WHO criteria for CML, PV, MDS, PMF or over myeloid neoplasm
• Demonstration of clonal cytogenetic marker or no evidence for a 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 (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

You may not qualify if…

• 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.
• Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
• 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) 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; 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 (see appendix B)
• 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

Where it is running

• Mayo Clinic — Scottsdale, Arizona, United States
• The Palo Alto Clinic — Palo Alto, 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
• University of Maryland — Baltimore, Maryland, 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 Pennsylvania — Philadelphia, Pennsylvania, United States
• University of Utah — Salt Lake City, Utah, United States
• Ospedale Riuniti de Bergamo — Bergamo, Italy, Italy
• University Of Florence — Florence, Italy, Italy
• Ospedale San Maartino Genova — Genova, Italy, Italy
• San Matteo Hospital — Pavia, Italy, Italy
• Universita Cattolica del Sacro Cuore — Rome, Italy, Italy

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.