High Risk Polycythemia VeraPhase 3NCT01259856
Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea in Polycythemia Vera (PV) and Essential Thrombocythemia (ET)
A Phase 3 study testing PEGASYS, Hydroxyurea and Aspirin in people with High Risk Polycythemia Vera and High Risk Essential Thrombocythemia, run by Ronald Hoffman at 25 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Polycythemia Vera, High Risk Essential Thrombocythemia
- What is being tested?
- PEGASYS, Hydroxyurea and Aspirin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 168 participants
- Where
- 25 sitesin 4 countries
- Study dates
- Sep 2011to 30 Jun 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 37Show fewer
- 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
Who cannot join
- (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
Show all 25Show fewer
- 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
- Thyroid dysfunction not adequately controlled
- Neutrophil count <1.5 x 10 to 9/L
- JAK2 exon 12 mutation: PV that lacks the JAK2V617F mutation but is characterized by the exon 12 mutation.
- Meets criteria for post PV or post ET-MF
- 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.
- Previous exposure to any formulation of pegylated interferon
- History of major organ transplantation
- History of uncontrolled severe seizure disorder
- Inability to give informed written consent
- Total bilirubin >1.5 x ULN (patients that have an isolated indirect bilirubin that causes total bilirubin to be elevated beyond 1.5 x ULN due to documented Gilbert's syndrome or hemolysis may be included). No detectable PNH (paroxysmal nocturnal hemoglobinuria) clone where tested
Trial locations and contacts
25 sites in 4 countries.
25 sites in 4 countries
United States16 sites
Emory Hospital
Atlanta, Georgia, 30322
John H. Stroger Hospital of Cook County
Chicago, Illinois, 60612
University of Illinois at Chicago
Chicago, Illinois, 60612
Geisinger Cancer Center
Danville, Pennsylvania, 17822
Duke University Medical Center
Durham, North Carolina, 27710
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical College
New York, New York, 10065
The Palo Alto Clinic
Palo Alto, California, 94301
University of Utah
Salt Lake City, Utah, 84132
Mayo Clinic
Scottsdale, Arizona, 85259
Stanford University School of Medicine
Stanford, California, 94305
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
University of Kansas Cancer Center
Westwood, Kansas, 66205
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157
Italy5 sites
Ospedale Riuniti de Bergamo
Bergamo
University Of Florence
Florence
Ospedale San Maartino Genova
Genova, 11632
San Matteo Hospital
Pavia, 27100
Universita Cattolica del Sacro Cuore
Rome, 00168
United Kingdom3 sites
Belfast City Hospital
Belfast, Northern Ireland, BT9 7AB
Heart of England NHS Foundation Trust
Birmingham, B9 5SS
Guy's and St. Thomas' NHS Foundation Trust
London, SE1 7EH
About this study
Official title: 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)
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.
Read the detailed description
The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are a group of clonal hematological malignancies that are characterized by a chronic course which can be punctuated by a number of disease related events including thrombosis, hemorrhage, pruritis and leukemic transformation. These disorders include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PM). Recently an acquired somatic mutation in the intracellular kinase, JAK2 (JAK2V617F) has been observed in 95% of patients with PV, 50% of patients with ET and 50% of patients with primary myelofibrosis. At present the chemotherapeutic agent hydroxyurea is the standard of care for high risk patients with PV. Concern exists about prolonged use of this drug leading to leukemia and the inability of hydroxyurea to eliminate the malignant clone.
Interferon (rIFN -2b), is a drug that appears to be non-leukemogenic, and may have a preferential activity on the malignant clone in PV, as suggested by cytogenetic remissions obtained in patients treated with rIFN -2b. Several investigators recently reported that patients with PV treated with rIFN -2b had lower JAK2V617F allele burdens as compared to a control group that included patients treated with phlebotomy, hydroxyurea, or anagrelide, or who remained untreated. The results confirm the hypothesis that rIFN -2b preferentially targets the malignant clone in PV and raises the possibility that the JAK2V617F allele burden, and a reversion of clonal hematopoiesis monitored in females by expression of X-chromosome polymorphic alleles maybe useful in monitoring minimal residual disease in PV patients.
Pegylated Interferon Alfa-2a (PEGASYS) has been demonstrated in phase II trials of patients with PV and ET to have clinical efficacy as measured by normalization of myeloproliferation, lack of vascular events while on therapy, and a decrease in the JAK2V617F allele burden. Overall the tolerability of the therapy was good, with each of these trials having a dropout rate secondary to toxicity of less than 10% of those enrolled. Although dropout rates for toxicity were low, that is not to say the therapy was without symptomatic toxicity, and indeed a spectrum of toxicities might be encountered and need to be weighed in the analysis of the net clinical benefit patients experience on a clinical trial with Pegylated Interferon Alfa-2a.
A new MPN assessment form will be utilized in this study. This 19 item instrument includes a previously validated 9 item brief fatigue inventory (BFI), symptoms related to splenomegaly, inactivity, cough, night sweats, pruritus, bone pains, fevers, weight loss, and an overall quality of life assessment. The instrument yields an independent result for each symptom (fatigue is a composite score), as this methodology (of linear analog scale assessment [LASA]) has proven very valid in the past. This instrument was validated prospectively (by comparison to a panel of instruments each containing an aspect of the MPN-SAF) for administration at a single time point.
This is a randomized trial between hydroxyurea and Pegylated Interferon Alfa-2a, it is an open label clinical trial in two independent disease strata: (1) high risk polycythemia vera and (2) high risk essential thrombocythemia.
- Being tested
- PEGASYS, Hydroxyurea, Aspirin
- Keywords
- Polycythemia vera, Essential thrombocythemia, Hydroxyurea, PEGASYS, Pegylated Interferon Alfa-2a
- Medical subject headings
- Polycythemia Vera, Thrombocythemia, Essential
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEGASYSDrug
Also called Pegylated Interferon Alfa-2a
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.
HydroxyureaDrug
Also called Hydroxycarbamide
Subjects will receive a 500mg tablet to be taken twice daily for up to 12 months of treatment.
AspirinDrug
Also called acetylsalicylic acid
Subject will be asked to take 81 to 100mg per day for the 12 months of the study treatment.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Hydroxyurea; Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 months
Secondary outcomes (6)
Number of Participants With Grade 3 and Grade 4 Hematological and Non-hematological Events
Number of Participants with Grade 3 and Grade 4 Hematological and Non-hematological Events using the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 to assess the toxicity, safety and tolerability of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea).
Measured: 4 years
Change in the Total Symptom Score (TSS)
Change in the Total Symptom Score which assessed improvement in disease symptoms measured by the change in TSS from the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) instrument being used in this study from baseline to 12 months. This 19 item instrument includes the previously validated 9 item brief fatigue inventory (BFI), symptoms related to splenomegaly, inactivity, cough, night sweats, pruritus, bone pains, fevers, weight loss, and an overall quality of life assessment. Each item is scored from 0-10 with full scale from 0-190, with higher scores mean worse symptoms.
Measured: baseline and 12 months
JAK2 Allele Burden
To compare the impact of therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) on key biomarkers of the disease(s) by measuring the JAK2 allele burden.
Measured: 4 years
Allele Burden
The impact of PEGASYS on JAK2 will be measured by the allele burden; hematopoietic cell clonality will be measured by whether patients with clonal disease return to polyclonal; bone marrow histopathology will be measured by going from abnormal to normal; cytogenetic abnormalities will be measured by seeing if the cytogenetics go from abnormal to normal.To compare the impact of therapy on JAK2-V617F (JAK2), CALR, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities.
Measured: 4 years
Number of Participants With Progression of Disease or Death
Survival and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation after therapy
To estimate survival and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation after therapy (Pegylated Interferon Alfa-2a vs. Hydroxyurea) by capturing the rate of progression to a more advanced myeloid malignancy.
Measured: 4 years
Number of Participants With Major Cardiovascular Events After Therapy
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2010 (estimated)
- Study startSep 2011
- Primary completion30 Jun 2017
- Study completion30 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for High Risk Polycythemia VeraStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ronald Hoffman
- Sponsor type
- University, hospital or other
- Collaborators
- Myeloproliferative Disorders-Research Consortium, National Cancer Institute (NCI), Roche Pharma AG
- Responsible party
- Sponsor-investigator, Ronald Hoffman, Icahn School of Medicine at Mount Sinai
- Investigators
- Ronald Hoffman, MD, Study chair, Icahn School of Medicine at Mount SinaiClaire Harrison, MD, Study chair, Guy's and St Thomas' NHS Foundation TrustRuben Mesa, MD, Study chair, Mayo ClinicJean-Jacques Kiladjian, MD, Study chair, Hopitaux de ParisMary Frances McMullin, MD, Study chair, Belfast Health and Social Care TrustJohn Mascarenhas, MD, Study chair, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01259856
- Sponsor's protocol ID
- GCO 09-1300-00002
- Other IDs
- P01CA108671, MPD-RC 112
- Status last verified
- Apr 2019
- First submitted
- 7 Dec 2010
- Last updated
- 30 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 40775758Mascarenhas 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.
PubMed 35007321Yacoub 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.
PubMed 31515250
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01259856
- Acronym / sponsor ID
- GCO 09-1300-00002
- Keywords
- Polycythemia vera, Essential thrombocythemia, Hydroxyurea, PEGASYS, Pegylated Interferon Alfa-2a
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- Ronald HoffmanUniversity, hospital or other
- Collaborators
- Myeloproliferative Disorders-Research Consortium, National Cancer Institute (NCI), Roche Pharma AG
- Study start
- Sep 2011
- Primary completion
- 30 Jun 2017 (actual)
- Study completion
- 30 Jun 2017 (actual)
- First posted
- 14 Dec 2010 (estimated)
- Results
- Posted 24 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are a group of clonal hematological malignancies that are characterized by a chronic course which can be punctuated by a number of disease related events including thrombosis, hemorrhage, pruritis and leukemic transformation. These disorders include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PM). Recently an acquired somatic mutation in the intracellular kinase, JAK2 (JAK2V617F) has been observed in 95% of patients with PV, 50% of patients with ET and 50% of patients with primary myelofibrosis. At present the chemotherapeutic agent hydroxyurea is the standard of care for high risk patients with PV. Concern exists about prolonged use of this drug leading to leukemia and the inability of hydroxyurea to eliminate the malignant clone.
Interferon (rIFN -2b), is a drug that appears to be non-leukemogenic, and may have a preferential activity on the malignant clone in PV, as suggested by cytogenetic remissions obtained in patients treated with rIFN -2b. Several investigators recently reported that patients with PV treated with rIFN -2b had lower JAK2V617F allele burdens as compared to a control group that included patients treated with phlebotomy, hydroxyurea, or anagrelide, or who remained untreated. The results confirm the hypothesis that rIFN -2b preferentially targets the malignant clone in PV and raises the possibility that the JAK2V617F allele burden, and a reversion of clonal hematopoiesis monitored in females by expression of X-chromosome polymorphic alleles maybe useful in monitoring minimal residual disease in PV patients.
Pegylated Interferon Alfa-2a (PEGASYS) has been demonstrated in phase II trials of patients with PV and ET to have clinical efficacy as measured by normalization of myeloproliferation, lack of vascular events while on therapy, and a decrease in the JAK2V617F allele burden. Overall the tolerability of the therapy was good, with each of these trials having a dropout rate secondary to toxicity of less than 10% of those enrolled. Although dropout rates for toxicity were low, that is not to say the therapy was without symptomatic toxicity, and indeed a spectrum of toxicities might be encountered and need to be weighed in the analysis of the net clinical benefit patients experience on a clinical trial with Pegylated Interferon Alfa-2a.
A new MPN assessment form will be utilized in this study. This 19 item instrument includes a previously validated 9 item brief fatigue inventory (BFI), symptoms related to splenomegaly, inactivity, cough, night sweats, pruritus, bone pains, fevers, weight loss, and an overall quality of life assessment. The instrument yields an independent result for each symptom (fatigue is a composite score), as this methodology (of linear analog scale assessment [LASA]) has proven very valid in the past. This instrument was validated prospectively (by comparison to a panel of instruments each containing an aspect of the MPN-SAF) for administration at a single time point.
This is a randomized trial between hydroxyurea and Pegylated Interferon Alfa-2a, it is an open label clinical trial in two independent disease strata: (1) high risk polycythemia vera and (2) high risk essential thrombocythemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PEGASYS | Experimental | Drug: PEGASYS, Drug: AspirinThe 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. |
| Hydroxyurea | Active comparator | Drug: Hydroxyurea, Drug: AspirinSubjects will receive a 500mg tablet to be taken twice daily for up to 12 months of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- 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)
- Essential Thrombocythemia (all 6 criteria required)
- Other Inclusion criteria (Both Strata)
Key exclusion criteria (25 listed)
- (ANY of the following, both strata)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEGASYSAlso: Pegylated Interferon Alfa-2aThe 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 |
| HydroxyureaAlso: HydroxycarbamideSubjects will receive a 500mg tablet to be taken twice daily for up to 12 months of treatment. | Drug | Hydroxyurea |
| AspirinAlso: acetylsalicylic acidSubject will be asked to take 81 to 100mg per day for the 12 months of the study treatment. | Drug | Hydroxyurea, PEGASYS |
Primary outcome
Number of Participants With Complete Remission (CR)
Time frame: 12 months
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.
Number of Participants With Partial Remission (PR)
Time frame: 12 months
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.
6 secondary outcomes
Number of Participants With Grade 3 and Grade 4 Hematological and Non-hematological Events
Time frame: 4 years
Change in the Total Symptom Score (TSS)
Time frame: baseline and 12 months
JAK2 Allele Burden
Time frame: 4 years
Allele Burden
Time frame: 4 years
Number of Participants With Progression of Disease or Death
Time frame: 4 years
Number of Participants With Major Cardiovascular Events After Therapy
Time frame: 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40775758Thanarajasingam 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.
- Derived from this study: PubMed 35007321Mascarenhas 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.
- Derived from this study: PubMed 31515250Yacoub 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald Hoffman, MD study chair
Icahn School of Medicine at Mount Sinai
Claire Harrison, MD study chair
Guy's and St Thomas' NHS Foundation Trust
Ruben Mesa, MD study chair
Mayo Clinic
25 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PEGASYS, Hydroxyurea and Aspirin in people with High Risk Polycythemia Vera and High Risk Essential Thrombocythemia, run by Ronald Hoffman at 25 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 37 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Italy, United Kingdom, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Complete Remission (CR) (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01259856, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2019.