Efficacy and Safety of Pegylated Interferon Alfa in Polycythemia Vera

Polycythemia Vera Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00241241
• Other study ID #: PVN1
• Status: Completed
• Phase: Phase 2
• First received: October 17, 2005
• Last updated: October 20, 2015
• Start date: September 2004
• Est. completion date: January 2008

Study information

• Verified date: October 2015
• Source: PV-Nord
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 2008
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

Drug:
• pegylated interferon-alfa 2a

Locations

Country	Name	City	State
France	Hopital Avicenne	Bobigny
France	Hopital Huriez	Lille
France	Hopital Dupuytren	Limoges
France	Hopital Lariboisiere	Paris
France	Hopital Saint-Louis	Paris

Sponsors (1)

Lead Sponsor	Collaborator
PV-Nord

Country where clinical trial is conducted

France, 

References & Publications (5)

Berk PD, Goldberg JD, Donovan PB, Fruchtman SM, Berlin NI, Wasserman LR. Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol. 1986 Apr;23(2):132-43. — View Citation

Fruchtman SM, Mack K, Kaplan ME, Peterson P, Berk PD, Wasserman LR. From efficacy to safety: a Polycythemia Vera Study group report on hydroxyurea in patients with polycythemia vera. Semin Hematol. 1997 Jan;34(1):17-23. Review. — View Citation

Kiladjian JJ, Bernard JF, Fenaux P. Is life expectancy of polycythemia vera patients clearly different from that of the general population? Am J Med. 2005 May;118(5):565; author reply 565-6. — View Citation

Lengfelder E, Berger U, Hehlmann R. Interferon alpha in the treatment of polycythemia vera. Ann Hematol. 2000 Mar;79(3):103-9. Review. — View Citation

Streiff MB, Smith B, Spivak JL. The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns. Blood. 2002 Feb 15;99(4):1144-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response rate after one year of treatment
Secondary	safety
Secondary	molecular response