Large-scale Trial Testing the Intensity of CYTOreductive Therapy in Polycythemia Vera (PV)

NCT01645124 | Terminated Phase 3

• 1 other identifier: FARM6YNXAN
• Study Type: interventional
• Target: 365
• Locations: 1 country
• Sites: 26

Brief Summary

CYTO-PV is a phase III Prospective, Randomized, Open-label, with Blinded Endpoint evaluation (PROBE), multi-center, clinical trial in patients with diagnosis of Polycythemia vera (PV) treated at the best of recommended therapies (e.g.adequate control of standard cardiovascular risk factors). Irrespective of randomized interventions, all patients will be administered low-dose aspirin (when not contraindicated), i.e.the standard antithrombotic treatment in PV patients. The purpose of this study to demonstrate that a more intensive cytoreductive therapy, plus low-dose aspirin when not contraindicated, with phlebotomy and/or hydroxyurea (HU), aimed at maintaining hematocrit (HCT) \< 45% is more effective than a less intensive cytoreduction (either with phlebotomy or HU plus low-dose aspirin when not contraindicated) maintaining HCT in the range of 45-50% in the reduction of CV deaths plus thrombotic events (stroke, acute coronary syndrome \[ACS\], transient ischemic attack \[TIA\], pulmonary embolism \[PE\], splanchnic thrombosis, deep vein thrombosis \[DVT\], and any other clinically relevant thrombotic event), in patients with Polycythemia Vera treated at the best of recommended therapies (e.g. adequate control of standard cardiovascular risk factors).

Conditions

Polycythemia Vera

Keywords

Polycythemia; Hematocrit; Thrombosis

Outcome Measures

Primary Outcomes (1)

• Reduction of PEP (Primary End Point)defined as CV deaths plus thrombotic events

  To demonstrate that in patients with PV treatment with aggressive cytoreductive therapy aimed at maintaining HCT \< 45% is more effective than cytoreductive therapy aimed at maintaining HCT between 45 and 50% in the reduction CV deaths plus thrombotic events (PEP: stroke, acute coronary syndrome \[ACS\], transient ischemic attack \[TIA\], pulmonary embolism \[PE\], abdominal thrombosis, deep vein thrombosis \[DVT\], and peripheral arterial thrombosis). The minimum clinically relevant beneficial effect is set at a 30% reduction of risk of the PEP.

  Expected average of 5 years

Secondary Outcomes (1)

• PEP plus minor thrombosis, hospitalization and malignancy

  Expected average of 5 years

Other Outcomes (1)

• Aadverse Events

  Expected average of 5 years

Study Arms (2)

Cytoreduction for HCT < 45%

ACTIVE COMPARATOR

Patients will be treated with phlebotomy and/or HU more intensively, with the goal to reach and maintain the target of hematocrit(HCT)below 45%. Phlebotomy should be performed initially by removing 250-500 ml of every other day or twice a week until the target HCT is obtained. Hydroxyurea (HU)should be administered initially at a dose of 0.5-1.0 g daily. Blood counts at regular intervals (monthly) will establish the frequency of future phlebotomies with the goal to maintain the target HCT. Supplemental iron therapy should not be given. Low-dose aspirin is the standard antithrombotic therapy in PV and will be administered to all patients with no contraindications to aspirin.

Drug: Hydroxyurea; Procedure: Phlebotomy

Cytoreduction for HCT between 45 and 50%

EXPERIMENTAL

Patients will be treated with phlebotomy and/or HU less intensively, with the goal to reach and maintain the target of hematocrit(HCT)between 45% and 50%. Phlebotomy should be performed initially by removing 250-500 ml of every other day or twice a week until the target HCT is obtained. Hydroxyurea (HU)should be administered initially at a dose of 0.5-1.0 g daily. Blood counts at regular intervals (monthly) will establish the frequency of future phlebotomies with the goal to maintain the target HCT. Supplemental iron therapy should not be given. Low-dose aspirin is the standard antithrombotic therapy in PV and will be administered to all patients with no contraindications to aspirin.

Drug: Hydroxyurea; Procedure: Phlebotomy

Interventions

Hydroxyurea DRUG

Cytoreduction for HCT < 45%; Cytoreduction for HCT between 45 and 50%

Phlebotomy PROCEDURE

Cytoreduction for HCT < 45%; Cytoreduction for HCT between 45 and 50%

Eligibility Criteria

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

You may qualify if:

• New diagnosis of PV according to WHO 2007 diagnostic criteria including Jak 2 V617F mutation status;
• Old diagnosis of PV confirmed with JAK-2 positivity and clinical course of the disease;
• Ability and willingness to comply with all study requirements;
• Written informed consent (obtained before any study specific procedure).

You may not qualify if:

• Pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception;
• Known hypersensitivity or contraindication to study treatments;
• Significant liver (AST or ALT \> 2.5 times ULN) or renal disease (creatinine \> 2 mg/ml);
• Presence of any life-threatening condition or of any disease (e.g. cancer) that is likely to significantly shorten life expectancy;
• History of active substance or alcohol abuse within the last year;
• Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol - Baseline and FUP visits schedule and assessments
• Logistic problem related to the patient.

Sponsors & Collaborators

• Consorzio Mario Negri Sud: lead
• Agenzia Italiana del Farmaco: collaborator
• A.O. Ospedale Papa Giovanni XXIII: collaborator

Study Sites (26)

Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona

Ancona, Ancona, 60020, Italy

Location

Azienda Ospedaliera Universitaria Ospedale Consorziale Policlinico di Bari

Bari, Bari, 70124, Italy

Location

Azienda Ospedali Riuniti di Bergamo

Bergamo, Bergamo, 24128, Italy

Location

Azienda Unità Sanitaria Locale di Brindisi BR/1- Ospedale "Di Summa - Perrino"

Brindisi, Brindisi, 72100, Italy

Location

Ospedale Armando Businco

Cagliari, Cagliari, 09121, Italy

Location

Azienda Ospedaliera Universitaria-'Policlinico- Vittorio Emanuele'-Ospedale Ferrarotto Alessi di Catania

Catania, Catania, 95124, Italy

Location

Azienda Ospedaliera S. Croce e Carle di Cuneo

Cuneo, Cuneo, 12100, Italy

Location

Azienda Ospedaliera Universitaria Careggi di Firenze

Florence, Firenze, 50134, Italy

Location

IRCCS Ospedale Casa Sollievo della Sofferenza di San Giovanni Rotondo

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Martino di Messina

Messina, Messina, 98122, Italy

Location

Fondazione IRCSS Cà Granda- Ospedale Maggiore Policlinico

Milan, Milano, 20122, Italy

Location

Ospedale S.Raffaele

Milan, Milano, 20132, Italy

Location

Ospedale S.Gerardo di Monza

Monza, Monza, 20900, Italy

Location

Azienda Ospedaliera Universitaria'Maggiore della Carità' di Novara

Novara, Novara, 28100, Italy

Location

Università di Padova

Padua, Padova, 35128, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico Giaccone di Palermo

Palermo, Palermo, 90127, Italy

Location

IRCCS Policlinico S. Matteo di Pavia

Pavia, Pavia, 27100, Italy

Location

Azienda Ospedaliera S. Salvatore, Presidio San Salvatore Muraglia

Pesaro, Pesaro, 61100, Italy

Location

IRCCS Centro di Riferimento Oncologico di Basilicata (CROB)

Rionero in Vulture, Potenza, 85028, Italy

Location

AUSL 4 Prato, Ospedale "Misericordia e Dolce" di Prato

Prato, Prato, 59100, Italy

Location

Ospedale di S.Maria Nuova

Reggio Emilia, Reggio Emilia, 42100, Italy

Location

IRCCS Istituto Regina Elena (IFO)

Roma, Roma, 00144, Italy

Location

Università degli Studi di Roma "La Sapienza"

Roma, Roma, 00161, Italy

Location

Policlinico Universitario Gemelli di Roma

Roma, Roma, 00168, Italy

Location

Azienda Ospedaliero-Universitaria San Luigi Gonzaga di Orbassano

Orbassano, Torino, 10043, Italy

Location

Ospedale San Bortolo di Vicenza

Vicenza, Vicenza, 36100, Italy

Location

Related Publications (1)

• Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013 Jan 3;368(1):22-33. doi: 10.1056/NEJMoa1208500. Epub 2012 Dec 8.

  PMID: 23216616 DERIVED

MeSH Terms

Conditions

Polycythemia Vera; Polycythemia; Thrombosis

Interventions

Hydroxyurea; Phlebotomy

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Blood Specimen Collection; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Tiziano Barbui, MD

  A.O. Ospedale Papa Giovanni XXIII

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2012
• First Posted: July 20, 2012
• Study Start: May 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: July 1, 2012
• Last Updated: July 20, 2012

Record last verified: 2012-05

Locations

IT (26)