Efficacy and Safety of Pegylated Interferon Alfa in Polycythemia Vera

Study Overview
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Brief Summary
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Interferon alfa is an effective treatment of polycythemia vera (PV), but about 20% of patients discontinue their treatment because of side effects and treatment schedule (three times per week administration). The pegylated form of interferon alfa-2a has shown a better tolerance in hepatitis patients and is administered only once a week. The purpose of this study is to determine efficacy and safety of pegylated interferon alfa-2a in the treatment of PV patients.

Detailed Description
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The aim of PV treatment is to reduce the risk of vascular thrombosis without enhancing the long-term risk of evolution toward myelofibrosis or MDS/AL. Although currently controversial, phlebotomies have been shown in the old PVSG01 study to increase the risk of both thrombosis and myelofibrosis. On the other hand, currently available cytoreductive treatments have been shown to efficiently reduce the thrombotic risk, but were demonstrated (32P, busulfan, chlorambucil) or suspected (pipobroman, hydroxyurea) to enhance the risk of evolution to MDS/AL. In fact, the main widely used cytoreductive treatment, when indicated, is hydroxyurea (HU). This drug is very efficient to control myeloproliferation with a response rate of 80 to 90%. It is generally well tolerated, even if long term toxicity leads to treatment change in 10% of cases. Although no prospective study has yet clearly demonstrated its leukemogenic potential in PV, a non-leukemogenic alternative treatment is highly warranted, especially for younger patient. Interferon (IFN) alpha is a promising agent in PV both because of good efficacy and absence of leukemogenic risk. Expanded experience with IFN-alpha was recently reported, showing a control of erythrocytosis in approximately 75% of patients. A similar percentage of patients also have resolution of disease-related symptoms, in particular a reduction in spleen size and relief from intractable pruritus. In some cases, long-term persisting remissions after treatment discontinuation have been observed as well as demonstration of eradication of the myeloproliferative clone. However, 20% of patients may not tolerate the treatment because of side effects. Furthermore, the treatment schedule (three times per week administration) may be a factor reducing long-term compliance to this drug. In this regard, pegylated-IFN could be a major drug in PV. The weekly administration and better tolerance by comparison to IFN reported in hepatitis patients could allow to obtain results similar to chemotherapy in terms of compliance to treatment and efficacy, with a major advantage, its lack of mutagenicity.

Official Title
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Multicenter Phase 2 Study of Efficacy and Safety of Pegylated Interferon-alfa 2a in Polycythemia Vera Patients

Conditions
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Polycythemia Vera

Intervention / Treatment
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* Drug: pegylated interferon-alfa 2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: polycythemia vera diagnosed according to PVSG criteria, modified by Pearson Previously untreated patients or patients treated by phlebotomy only or HU or pipobroman for less than 2 years Age 18 to 65 years Signed informed consent Exclusion Criteria: Contra indication for interferon Severe renal or liver disease ECOG performance status > 2 Pregnancy Uncontrolled endocrine disorders except well regulated hyperthyroidism and diabetes Severe concomitant heart failure or psychiatric disorder Patients receiving an other investigational treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pegylated interferon-alfa 2a|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate after one year of treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety |  |  | 
| molecular response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myeloproliferative disorder, polycythemia vera, interferon