Single Arm Salvage Therapy With Pegylated Interferon Alfa-2a for Patients With High Risk Polycythemia Vera or High Risk Essential Thrombocythemia Who Are Either Hydroxyurea Resistant or Intolerant or Have Had Abdominal Vein Thrombosis

Status: Completed
Location: See all (21) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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.

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

• 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

• 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)

• WBC < 2.5 x 109/L or Hgb < 11g/dl at any dose of hydroxyurea not to exceed 2g/day.

• Progressive splenomegaly or hepatomegaly (> 5cm from initiation of hydroxyurea) or the appearance of new splenomegaly or hepatomegaly while on MTD of hydroxyurea.

• Not achieving a Hct < 45% in order to eliminate the need for supplemental phlebotomies after 3 months of at least 2g/day or MTD of hydroxyurea.

• Not achieving a WBC of < 10 x 109/L after 3 months of at least 2g/day or MTD of hydroxyurea.

• Having a platelet count < 100 x 109/L on hydroxyurea at any dose without eliminating the need for supplemental phlebotomy or having progressive splenomegaly as defined above.

• Development of a major thrombotic episode (CVA, myocardial infarction, severe migraines requiring medication, abdominal vein thrombosis, deep vein thrombosis) while being treated with maximal tolerated doses of hydroxyurea.

• 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

Locations
United States
Arizona
Mayo Clinic
Scottsdale
California
The Palo Alto Clinic
Palo Alto
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
Maryland
University of Maryland
Baltimore
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
University of Pennsylvania
Philadelphia
Utah
University of Utah
Salt Lake City
Other Locations
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
Time Frame
Start Date: September 2011
Completion Date: December 2016
Participants
Target number of participants: 135
Treatments
Experimental: PEGASYS
Patient will start at 45 micrograms per week and gradually increase to 180 micrograms per week. Pegasys will be supplied in prefilled syringes and are to be given subcutaneously.
Active Comparator: Aspirin
81 or 100 mg daily.
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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