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

Status: Completed
Location: See all (25) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• 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

• Diabetes or hypertension requiring pharmacological therapy for > 6 months

• Other Inclusion criteria (Both Strata)

• Diagnosed less than 5 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

Locations
United States
Arizona
Mayo Clinic
Scottsdale
California
USC Norris Comprehensive Cancer Center
Los Angeles
The Palo Alto Clinic
Palo Alto
Stanford University School of Medicine
Stanford
Washington, D.c.
Georgetown University Medical Center
Washington
Georgia
Emory Hospital
Atlanta
Illinois
John H. Stroger Hospital of Cook County
Chicago
University of Illinois at Chicago
Chicago
Kansas
University of Kansas Cancer Center
Westwood
North Carolina
Duke University Medical Center
Durham
Wake Forest University Baptist Medical Center
Winston-salem
New York
Icahn School of Medicine at Mount Sinai
New York
Memorial Sloan-Kettering Cancer Center
New York
Weill Cornell Medical College
New York
Pennsylvania
Geisinger Cancer Center
Danville
Utah
University of Utah
Salt Lake City
Other Locations
France
Hopitaux de Paris
Paris
Italy
Ospedale Riuniti de Bergamo
Bergamo
University Of Florence
Florence
Ospedale San Maartino Genova
Genova
San Matteo Hospital
Pavia
Universita Cattolica del Sacro Cuore
Rome
United Kingdom
Belfast City Hospital
Belfast
Heart of England NHS Foundation Trust
Birmingham
Guy's and St. Thomas' NHS Foundation Trust
London
Time Frame
Start Date: September 2011
Completion Date: June 30, 2017
Participants
Target number of participants: 168
Treatments
Experimental: PEGASYS
The subject will begin receiving the PEGASYS at a dose level of 45 micrograms weekly and gradually get increased to the maximum dose of 180 micrograms per week. The dose will be administered by prefilled syringes that will be injected subcutaneously. Subjects will receive therapy for up to 12 months.
Active Comparator: Hydroxyurea
Subjects will receive a 500mg tablet to be taken twice daily for up to 12 months of treatment.
Sponsors
Collaborators: Roche Pharma AG, Myeloproliferative Disorders-Research Consortium, National Cancer Institute (NCI)
Leads: Ronald Hoffman

This content was sourced from clinicaltrials.gov

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