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

NCT01259856 | Completed Phase 3 Results DMC

• 3 other identifiers: GCO 09-1300-00002P01CA108671MPD-RC 112
• Study Type: interventional
• Target: 168
• Locations: 4 countries
• Sites: 25

Brief 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.

Conditions

High Risk Polycythemia Vera; High Risk Essential Thrombocythemia

Keywords

Polycythemia vera; Essential thrombocythemia; Hydroxyurea; PEGASYS; Pegylated Interferon Alfa-2a

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Complete Remission (CR)

  Number of participants with Complete Remission after 12 months of therapy assessed by hematologic response rates two strata of patients with high risk polycythemia vera (PV) or high risk essential thrombocythemia (ET). Complete remission means no evidence of disease.

  12 months

• Number of Participants With Partial Remission (PR)

  Number of participants with Partial Remission after 12 months of therapy assessed by hematologic response rates two strata of patients with high risk polycythemia vera (PV) or high risk essential thrombocythemia (ET). Partial Remission means decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment.

  12 months

Secondary Outcomes (6)

• Number of Participants With Grade 3 and Grade 4 Hematological and Non-hematological Events

  4 years

• Change in the Total Symptom Score (TSS)

  baseline and 12 months

• JAK2 Allele Burden

  4 years

• Allele Burden

  4 years

• Number of Participants With Progression of Disease or Death

  4 years

Study Arms (2)

PEGASYS

EXPERIMENTAL

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.

Drug: PEGASYS; Drug: Aspirin

Hydroxyurea

ACTIVE COMPARATOR

Subjects will receive a 500mg tablet to be taken twice daily for up to 12 months of treatment.

Drug: Hydroxyurea; Drug: Aspirin

Interventions

PEGASYS DRUG

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.

Also known as: Pegylated Interferon Alfa-2a

PEGASYS

Hydroxyurea DRUG

Subjects will receive a 500mg tablet to be taken twice daily for up to 12 months of treatment.

Also known as: Hydroxycarbamide

Hydroxyurea

Aspirin DRUG

Subject will be asked to take 81 to 100mg per day for the 12 months of the study treatment.

Also known as: acetylsalicylic acid

Hydroxyurea; PEGASYS

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 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:

You may not qualify if:

• (ANY of the following, both strata)
• Known to meet the criteria for primary myelofibrosis (as opposed to ET) by WHO 2008
• Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
• Any contraindications to pegylated interferon or hydroxyurea
• Presence of any life-threatening co-morbidity
• History of active substance or alcohol abuse within the last year
• Subjects who are pregnant, lactating or of reproductive potential and not practicing an effective means of contraception
• History of psychiatric disorder (e.g. depression) 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)
• Hypersensitivity to interferon alfa
• Hepatitis B or C infection (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

Sponsors & Collaborators

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

Study Sites (25)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

The Palo Alto Clinic

Palo Alto, California, 94301, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, 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

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 Utah

Salt Lake City, Utah, 84132, United States

Location

Hopitaux de Paris

Paris, 75010, France

Location

Ospedale Riuniti de Bergamo

Bergamo, Italy

Location

University Of Florence

Florence, Italy

Location

Ospedale San Maartino Genova

Genova, 11632, Italy

Location

San Matteo Hospital

Pavia, 27100, Italy

Location

Universita Cattolica del Sacro Cuore

Rome, 00168, Italy

Location

Belfast City Hospital

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

Heart of England NHS Foundation Trust

Birmingham, B9 5SS, United Kingdom

Location

Guy's and St. Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

Related Publications (3)

• 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

• Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, Harrison CN, McMullin MF, Vannucchi AM, Ewing J, O'Connell CL, Kiladjian JJ, Mead AJ, Winton EF, Leibowitz DS, De Stefano V, Arcasoy MO, Kessler CM, Catchatourian R, Rondelli D, Silver RT, Bacigalupo A, Nagler A, Kremyanskaya M, Levine MF, Arango Ossa JE, McGovern E, Sandy L, Salama ME, Najfeld V, Tripodi J, Farnoud N, Penson AV, Weinberg RS, Price L, Goldberg JD, Barbui T, Marchioli R, Tognoni G, Rampal RK, Mesa RA, Dueck AC, Hoffman R. A randomized phase 3 trial of interferon-alpha vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood. 2022 May 12;139(19):2931-2941. doi: 10.1182/blood.2021012743.

  PMID: 35007321 DERIVED

• Yacoub A, Mascarenhas J, Kosiorek H, Prchal JT, Berenzon D, Baer MR, Ritchie E, Silver RT, Kessler C, Winton E, Finazzi MC, Rambaldi A, Vannucchi AM, Leibowitz D, Rondelli D, Arcasoy MO, Catchatourian R, Vadakara J, Rosti V, Hexner E, Kremyanskaya M, Sandy L, Tripodi J, Najfeld V, Farnoud N, Papaemmanuil E, Salama M, Singer-Weinberg R, Rampal R, Goldberg JD, Barbui T, Mesa R, Dueck AC, Hoffman R. Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. Blood. 2019 Oct 31;134(18):1498-1509. doi: 10.1182/blood.2019000428.

  PMID: 31515250 DERIVED

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential

Interventions

peginterferon alfa-2a; Hydroxyurea; 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)

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

Results Point of Contact

• Title: Dr. Ronald Hoffman
• Organization: Icahn School of Medicine at Mount Sinai

ronald.hoffman@mssm.edu

212-241-2296

Study Officials

• Ronald Hoffman, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Claire Harrison, MD

  Guy's and St Thomas' NHS Foundation Trust

  STUDY CHAIR

• Ruben Mesa, MD

  Mayo Clinic

  STUDY CHAIR

• Jean-Jacques Kiladjian, MD

  Hopitaux de Paris

  STUDY CHAIR

• Mary Frances McMullin, MD

  Belfast Health and Social Care Trust

  STUDY CHAIR

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: 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 7, 2010
• First Posted: December 14, 2010
• Study Start: September 1, 2011
• Primary Completion: June 30, 2017
• Study Completion: June 30, 2017
• Last Updated: April 30, 2019
• Results First Posted: July 24, 2018

Record last verified: 2019-04

Locations

GB (3); IT (5); US (16); FR (1)