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

NCT01259817 | Completed Phase 2 DMC

• 3 other identifiers: GCO 09-1300 001P01CA108671MPD-RC 111
• Study Type: interventional
• Target: 135
• Locations: 2 countries
• Sites: 21

Brief 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.

Conditions

High Risk Polycythemia Vera; High Risk Essential Thrombocythemia

Keywords

Polycythemia Vera; Essential Thrombocythemia; Hydroxyurea Resistant; Abdominal Vein Thrombosis; PEGASYS

Outcome Measures

Primary Outcomes (1)

• Evaluate the ability of Pegylated Interferon Alfa-2a to achieve Complete Response or Partial Response in patients with (1) high risk polycythemia vera or (2) high risk essential thrombocythemia or (3) splanchnic vein thrombosis

  4 years

Secondary Outcomes (6)

• To evaluate the toxicity and tolerability of therapy Pegylated Interferon Alfa-2a in each of the 3 strata by recording the number of adverse events that occur during the study by using CTC 4.0 as the guide.

  4 years

• To measure the impact of Pegylated Interferon Alfa-2a on key biomarkers of the disease(s)by measuring the JAK2 allele burden.

  4 years

• To evaluate specific pre-defined toxicity and tolerance of Pegylated Interferon Alfa-2a through a sequential structured symptom assessment package of patient reported outcome instruments.

  4 years

• To estimate survival, and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation during therapy Pegylated Interferon Alfa-2a.

  4 years

• Estimate the observed incidence of major cardiovascular events during therapy Pegylated Interferon Alfa-2a.

  4 years

Study Arms (2)

PEGASYS

EXPERIMENTAL

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.

Drug: PEGASYS

Aspirin

ACTIVE COMPARATOR

81 or 100 mg daily.

Drug: Aspirin

Interventions

PEGASYS DRUG

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.

Also known as: Pegylated Interferon Alfa-2a

PEGASYS

Aspirin DRUG

81 or 100 mg daily.

Also known as: acetylsalicylic acid

Aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

You may not qualify if:

• \> 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
• Patients cannot have any other form of chemotherapy for their MPD (other than hydroxyurea). Specifically prior interferon or JAK2 inhibitors are prohibited.

Sponsors & Collaborators

• Ronald Hoffman: lead
• Myeloproliferative Disorders-Research Consortium: collaborator
• National Cancer Institute (NCI): collaborator
• Roche Pharma AG: collaborator

Study Sites (21)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

The Palo Alto Clinic

Palo Alto, California, 94301, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Emory Hospital

Atlanta, Georgia, 30322, United States

Location

John H. Stroger Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Geisinger Cancer Center

Danville, Pennsylvania, 17822, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Ospedale Riuniti de Bergamo

Bergamo, Italy, Italy

Location

University Of Florence

Florence, Italy, Italy

Location

Ospedale San Maartino Genova

Genova, Italy, 11632, Italy

Location

San Matteo Hospital

Pavia, Italy, 27100, Italy

Location

Universita Cattolica del Sacro Cuore

Rome, Italy, Italy

Location

Related Publications (1)

• Thanarajasingam G, Bhatnagar V, Noble BN, Chen TY, Fiero MH, Hoffman R, Jeffery M, Mazza GL, Mascarenhas J, Mesa R, Murugappan M, Ross J, Sidana S, Warsame R, Kluetz PG, Dueck AC. Longitudinal graphics of patient-reported physical function in patients treated for hematologic malignancies. BMC Med Res Methodol. 2025 Aug 7;25(1):189. doi: 10.1186/s12874-025-02617-y.

  PMID: 40775758 DERIVED

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential

Interventions

peginterferon alfa-2a; Aspirin

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Ellen Ritchie, MD

  Myeloproliferative Disorders-Research Consortium

  PRINCIPAL INVESTIGATOR

• Alessandro Rambaldi, MD

  Myeloproliferative Disorders-Research Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine, Hematology and Medical Oncology

Study Record Dates

• First Submitted: December 6, 2010
• First Posted: December 14, 2010
• Study Start: September 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 11, 2017

Record last verified: 2017-01

Locations

IT (5); US (16)