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Trial record 24 of 234 for:    "Polycythemia vera"

The Benefit/Risk Profile of AOP2014 in Low-risk Patients With PV (Low-PV)

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ClinicalTrials.gov Identifier: NCT03003325
Recruitment Status : Recruiting
First Posted : December 28, 2016
Last Update Posted : August 10, 2017
Sponsor:
Collaborator:
AOP Orphan Pharmaceuticals AG
Information provided by (Responsible Party):
Fondazione per la Ricerca Ospedale Maggiore

Brief Summary:
The Low-PV study is a multicenter, phase II, randomized trial aimed to assess whether the addition of Pegylated Proline-interferon-alpha-2b to the best therapeutic current strategy available based on phlebotomies and low dose acetylsalicylic acid (ASA) could improve the efficacy of treatment of patients with PV at low risk of thrombosis (younger than 60 years and without prior vascular events), in term of control of recommended level of hematocrit < 45%, over a period of 12 months.

Condition or disease Intervention/treatment Phase
Polycythemia Vera Drug: AOP2014 Procedure: Phlebotomies Drug: ASA Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Benefit/Risk Profile of Pegylated Proline-Interferon Alpha-2b (AOP2014) Added to the Best Available Strategy Based on Phlebotomies in Low-risk Patients With Polycythemia Vera (PV). The Low-PV Randomized Trial
Actual Study Start Date : February 2, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Active Comparator: Phlebotomies + ASA
Conventional treatment based on phlebotomies and low dose (100 mg) of acetylsalicylic acid (ASA)
Procedure: Phlebotomies
According to current common clinical practice the regimen must be selected accordingly to maintain the recommended level of HCT< 45%. Once normalization of the hematocrit has been achieved, blood counts at regular intervals (every 4 weeks) will establish the frequency of future phlebotomies. Sufficient blood should be removed to maintain the hematocrit below 45%.
Other Name: blood removing

Drug: ASA
100 mg/daily of ASA is recommended (when there are not contraindications) according with current guidelines for this risk class of patients
Other Name: Acetylsalicylic Acid

Experimental: Phlebotomies + ASA + AOP2014
Conventional treatment based on phlebotomies, low dose (100 mg) of acetylsalicylic acid (ASA) plus the addition of 100 µg of Pegylated Proline-Interferon alpha-2b (AOP2014) once every 14 days (subcutaneously).
Drug: AOP2014
AOP2014 will be supplied to the patients as pre-filled auto-injection pens, containing 250 µg of active drug (0.5 ml solution for injection). One pen may be used twice within a time period of 4 weeks. Hence investigators will provide one prefilled pen at every monthly visit. AOP2014 will be self-injected subcutaneously by patients once every 14 days at the single doses of 100 µg (0.2 ml).
Other Name: Pegylated-Proline-Interferon α-2b, P1101

Procedure: Phlebotomies
According to current common clinical practice the regimen must be selected accordingly to maintain the recommended level of HCT< 45%. Once normalization of the hematocrit has been achieved, blood counts at regular intervals (every 4 weeks) will establish the frequency of future phlebotomies. Sufficient blood should be removed to maintain the hematocrit below 45%.
Other Name: blood removing

Drug: ASA
100 mg/daily of ASA is recommended (when there are not contraindications) according with current guidelines for this risk class of patients
Other Name: Acetylsalicylic Acid




Primary Outcome Measures :
  1. Number of patients who maintains the median value of HCT< 45%, along 12 months, on number of patients randomized in each arm, per cent [ Time Frame: 12 months ]

    For each patient the median value of HCT percentage will be calculated from all measurements detected and reported every month (from baseline to 12-month visit or study end). A patient will be defined as responder (achieving PEp) when he maintains the median value of HCT < 45%, after undergoing treatments according to this protocol, for up 12 months.

    A patient will be defined as non-responder (not achieving PEp) when

    1. Does not maintain the median value of HCT < 45%, after undergoing treatments according to this protocol, for up 12 months, or
    2. Is in need of any additional chemotherapeutic and/or cytoreductive treatment aimed to manage disease due to disease progression.


Secondary Outcome Measures :
  1. Median number of phlebotomies performed [ Time Frame: 12 months, 24 months ]
    1. The total number of phlebotomies will be calculated for each patients during 12 months of therapy (and then 24 months);
    2. Based on values obtained from point (1) in each arm-group of patients, the median number of phlebotomies performed in each therapy group will be calculated (and compared) after 12 and 24 months of therapy (or completion of the study)

  2. Number of patients achieving hematological response (as defined below in 'Description') on number of patients randomized in each arm, per cent, [ Time Frame: 12 months, 24 months ]
    For each patient the median value of HCT (%), absolute white blood cells (WBCs) count and absolute platelets (PLTs) count will be calculated from all measurements detected and reported at least every month (from baseline to 12-month visit and then to 24-month visit/study completion). A patient will be defined as achieving hematological response when the median values of HCT < 45%, WBCs count < 10 x10*9/L and PLTs count < 400 x10*9/L is observed after 12 months of therapy (or 24 months). The proportion of patients who maintains this response after 24 months (or study completion) will be calculated (and compared) in each arm.

  3. Proportion (rate per cent) of patients with not palpable spleen [ Time Frame: 12 months, 24 months ]
    The proportion (rate per cent) of patients with not palpable spleen will be calculated in each arm as the ratio of number of patients with resolution of splenomegaly or persistence of not palpable spleen at palpation with respect to baseline, on number of patients randomized in each arm, after 12 and 24 months (study completion) of therapy, per cent.

  4. Janus kinase-2 allele burden reduction or complete molecular remission [ Time Frame: 12 months, 24 months ]

    Quantitative Janus kinase-2 measurements (central lab facility) will be performed at baseline and after 12 months of therapy for all patients; Janus kinase-2 assessment will be performed also after 24 months for patients receiving interferon (experimental therapy). Reduction of allele burden in each patient (with respect to baseline) will be assessed according to Jovanovic et al, Leukemia 2013.

    The proportion (rate per cent) of patients with Janus kinase-2 allele burden reduction or remission will be calculated in each arm (and compared).


  5. Bone marrow histological remission [ Time Frame: 24 months ]
    Defined as presence of age-adjusted normocellularity and disappearance of trilinear hyperplasia, and absence of >grade 1 reticulin fibrosis. It will be assessed in each patient and then the proportion (rate per cent) of patients with bone marrow histological remission will be calculated in each arm (and compared).

  6. Incidence and frequence of thrombotic and hemorrhagic events occurred [ Time Frame: 12 months, 24 months ]
    The number of events will be recorded any time during the study in order to assess the frequency ,every 12 months and at completion of the study, and their incidence in each arm and whole population. Comparison between arms will be performed.

  7. Number of adverse events occurred [ Time Frame: 12 months, 24 months ]

    Incidence, causality and intensity of clinical relevant adverse events will be assessed in each arm and compared all over the study.

    The rate of assigned treatment withdrawal due to any protocol drug-related toxicity occurred any time will be compared. Number of adverse events, expressed as frequency in each arm, will be calculated (as ratio of number of patient experiencing adverse on the the number of patients randomized in each arm) and compared



Other Outcome Measures:
  1. Quality of Life (QoL) [ Time Frame: 12 months, 24 months ]
    Impact of PV and therapy on subjects will be evaluated through assessment of symptoms burden using Functional Assessment of cancer Therapy-Anaemia (FACT-An) and Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) questionnaires, that will be administered to subjects trimonthly



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-60 years
  • Diagnosis of Polycythemia Vera according to World Health Organization 2008 criteria
  • Diagnosis of Polycythemia Vera performed within 3 years prior inclusion in the study and never treated with cytoreductive drugs
  • HCT<45%
  • Ability and willingness to comply with all study requirements
  • Signed written informed consent.

Exclusion Criteria:

  • Any previous well documented cardiovascular PV-related events (see Appendix 1 for description)
  • Previous cytoreductive drugs
  • Known hypersensitivity or contraindications to the Investigational Medicinal Product (Pegylated Proline-Interferon alpha-2b) including:

evidence of severe retinopathy (e.g. cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension); thyroid dysfunction not adequately controlled; patients tested positively with Thyroglobulin antibody and / or TPOAb at screening; documented autoimmune disease at screening or in the medical history; history or presence of depression requiring treatment with antidepressant; any risk of suicide at screening or previous suicide attempts;

  • Previous exposure to a non-pegylated or pegylated interferon α
  • Clinically relevant pulmonary infiltrates, pneumonia, and pneumonitis
  • Systemic infections, e.g. hepatitis B, hepatitis C, or HIV at screening
  • Significant liver (AST or alanine aminotransferase > 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
  • Pregnant or lactating women and women*/men of childbearing potential who are not using or are not willing to use any effective means of contraception (i.e. sexual abstinence, hormonal contraceptive, intra-uterine device, barrier method such as diaphragms or condoms, surgical methods).

    • Pregnancy test will be performed in order to ascertain negativity of human chorionic gonadotropin (β-hCG) test and confirm that childbearing women are not pregnant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03003325


Contacts
Contact: Arianna Masciulli, PharmD 0352678926 amasciulli@asst-pg23.it
Contact: Roberta Porcino 0352678977 rporcino@asst-pg23.it

Locations
Italy
U.O. Ematologia, Ospedale Casa Sollievo della Sofferenza Istituto di Ricovero e Cura a Carattere Scientifico Recruiting
San Giovanni Rotondo, (FG) Puglia, Italy, 71013
Contact: Daniela Valente    0882410566    ematologia@operapadrepio.it   
Principal Investigator: Nicola Cascavilla, MD         
Sub-Investigator: Potito R Scalzulli, MD         
Azienda Ospedaliera Universitaria Federico II di Napoli Recruiting
Napoli, Campania, Italy, 80131
Contact: Marcello Tammaro, PharmD    0817462037    m.tammaro@gimema.it   
Principal Investigator: Fabrizio Pane, MD         
Sub-Investigator: Vincenzo Martinelli, MD         
Sub-Investigator: Novella Pugliese, MD         
Divisione Ematologia Policlinico S. Orsola - Malpighi Recruiting
Bologna, Emilia Romagna, Italy, 40138
Contact: Chiara De Maio    0512143151    chiara.demaio@unibo.it   
Principal Investigator: Michele Cavo, MD         
Sub-Investigator: Francesca Palandri, MD         
Sub-Investigator: Nicola Vianelli, MD         
Clinica Ematologica, Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia" Not yet recruiting
Udine, Friuli Venezia Giulia, Italy, 33100
Contact: Cristina D'Odorico    0432559620/559543    dodorico.cristina@aoud.sanita.fvg.it; tuniz.enrica@aoud.sanita.fvg.it; barazzutti.tullio@aoud.sanita.fvg.it   
Principal Investigator: Mario Tiribelli, MD         
Sub-Investigator: Federico De Marchi, MD         
Sub-Investigator: Domenico Penna, MD         
UCSC Ematologia, Fondazione Policlinico Universitario "Agostino Gemelli"Università Cattolica del Sacro Cuore Recruiting
Roma, Lazio, Italy, 00168
Contact: Denise Soldati    0630154968/4206    denise_soldati@outlook.it   
Principal Investigator: Valerio De Stefano, MD         
Sub-Investigator: Elena Rossi, MD         
Sub-Investigator: Silvia Betti, MD         
USC Ematologia, ASST Papa Giovanni XXIII Recruiting
Bergamo, Lombardia, Italy, 24127
Contact: Maria Luisa Ferrari    035 2673681    mlferrari@asst-pg23.it   
Principal Investigator: Alessandro Rambaldi, MD         
Sub-Investigator: Maria Chiara Finazzi, MD         
Divisione Oncoematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Recruiting
Milano, Lombardia, Italy, 20122
Contact: Silvia Artuso    0255033469    silvia.artuso@policlinico.mi.it   
Principal Investigator: Alessandra Iurlo, MD         
Sub-Investigator: Cristina Buccelli, MD         
Sub-Investigator: Daniele Cattaneo, MD         
Divisione Ematologia ASST, Grande Ospedale Metropolitano Niguarda Not yet recruiting
Milano, Lombardia, Italy, 20162
Contact: Ester Pungolino       ester.pungolino@ospedaleniguarda.it   
Principal Investigator: Ester Pungolino, MD         
Divisione Ematologia, ASST di MONZA - Ospedale San Gerardo di Monza Suspended
Monza, Lombardia, Italy, 20900
Divisione Ematologia, Fondazione IRCCS Policlinico San Matteo Active, not recruiting
Pavia, Lombardia, Italy, 27100
U.O. Ematologia, Ospedale di Circolo e Fondazione Macchi Varese Active, not recruiting
Varese, Lombardia, Italy, 21100
S.C. Ematologia Azienda Ospedaliera S. Croce e Carle Cuneo Recruiting
Cuneo, Piemonte, Italy, 12100
Contact: Laura Bertolotti    0171642228    bertolotti.l@ospedale.cuneo.it   
Principal Investigator: Davide Rapezzi, MD         
Sub-Investigator: Roberto Sorasio, MD         
SCDU Ematologia, A.O.U. Maggiore della Carità Active, not recruiting
Novara, Piemonte, Italy, 28100
S.C. Ematologia, AOU- Presidio Ospedaliero Molinette Active, not recruiting
Torino, Piemonte, Italy, 10126
U.O. Ematologia con Trapianto, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari Recruiting
Bari, Puglia, Italy, 70120
Contact: Marianna Gentile    0805592579    trials.ematba@gmail.com   
Principal Investigator: Giorgina Specchia, MD         
Sub-Investigator: Alessandra Ricco, MD         
Unità Operativa Complessa di Emostasi Azienda Ospedaliero-Universitario "Policlinico Vittorio-Emanuele - Presidio Ospedaliero Ferrarotto Active, not recruiting
Catania, Sicilia, Italy, 95124
UOC Ematologia, Azienda Ospedaliera Universitaria Policlinico "G. Martino" Recruiting
Messina, Sicilia, Italy, 98100
Contact: Oriana Bianco, MD    0902213253    orianaf.bianco@gmail.com   
Principal Investigator: Caterina Musolino, MD         
Sub-Investigator: Oriana Bianco, MD         
Sub-Investigator: Doriana Vaddinelli, MD         
Divisione Ematologia Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone" Palermo Not yet recruiting
Palermo, Sicilia, Italy, 90127
Contact: Cristina Riggio, MD    0916554403    cristina.riggio@gmail.com   
Principal Investigator: Sergio Siragusa, MD         
Sub-Investigator: Vincenzo Accurso Casteldaccia, MD         
Sub-Investigator: Clementina Caraccolo, MD         
SOD Ematologia AUOC Azienda Ospedaliero-Universitaria "Careggi" Active, not recruiting
Firenze, Toscana, Italy, 50134
Clinica Medica I Azienda Ospedaliera di Padova Not yet recruiting
Padova, Veneto, Italy, 35128
Contact: Irene Bertozzi    0498213293    irene.bertozzi@gmail.com   
Principal Investigator: Maria Luigia Randi, MD         
Divisione Ematologia, Ospedale Borgo Roma Recruiting
Verona, Veneto, Italy, 37134
Contact: Irene Rossi    0458126564    irene.rossi@crc.vr.it   
Principal Investigator: Massimiliano Bonifacio, MD         
Sub-Investigator: Luigi Scaffidi, MD         
Divisione Ematologia, Ospedale San Bortolo Recruiting
Vicenza, Veneto, Italy
Contact: Marco Ruggeri, MD       ruggeri@hemato.ven.it   
Principal Investigator: Marco Ruggeri, MD         
Sub-Investigator: Giuseppe Carli, MD         
Sub-Investigator: Omar Perbellini, MD         
Sponsors and Collaborators
Fondazione per la Ricerca Ospedale Maggiore
AOP Orphan Pharmaceuticals AG
Investigators
Study Chair: Tiziano Barbui, Professor Fondazione per la Ricerca Ospedale Maggiore di Bergamo (FROM)

Publications:
Emanuel RM, Dueck AC, Geyer HL, Kiladjian JJ, Slot S, Zweegman S, te Boekhorst PA, Commandeur S, Schouten HC, Sackmann F, Kerguelen Fuentes A, Hernández-Maraver D, Pahl HL, Griesshammer M, Stegelmann F, Doehner K, Lehmann T, Bonatz K, Reiter A, Boyer F, Etienne G, Ianotto JC, Ranta D, Roy L, Cahn JY, Harrison CN, Radia D, Muxi P, Maldonado N, Besses C, Cervantes F, Johansson PL, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson B, Ferrari ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Mesa RA. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol. 2012 Nov 20;30(33):4098-103. doi: 10.1200/JCO.2012.42.3863. Epub 2012 Oct 15. Erratum in: J Clin Oncol. 2012 Dec 20;30(36):4590. Ferarri, Maria L [corrected to Ferrari, Maria L].
Jovanovic JV, Ivey A, Vannucchi AM, Lippert E, Oppliger Leibundgut E, Cassinat B, Pallisgaard N, Maroc N, Hermouet S, Nickless G, Guglielmelli P, van der Reijden BA, Jansen JH, Alpermann T, Schnittger S, Bench A, Tobal K, Wilkins B, Cuthill K, McLornan D, Yeoman K, Akiki S, Bryon J, Jeffries S, Jones A, Percy MJ, Schwemmers S, Gruender A, Kelley TW, Reading S, Pancrazzi A, McMullin MF, Pahl HL, Cross NC, Harrison CN, Prchal JT, Chomienne C, Kiladjian JJ, Barbui T, Grimwade D. Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study. Leukemia. 2013 Oct;27(10):2032-9. doi: 10.1038/leu.2013.219. Epub 2013 Jul 17.

Responsible Party: Fondazione per la Ricerca Ospedale Maggiore
ClinicalTrials.gov Identifier: NCT03003325     History of Changes
Other Study ID Numbers: Low-PV
First Posted: December 28, 2016    Key Record Dates
Last Update Posted: August 10, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: No plan has been defined yet about sharing of IPD

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fondazione per la Ricerca Ospedale Maggiore:
low risk of thrombosis
Interferon

Additional relevant MeSH terms:
Polycythemia Vera
Polycythemia
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Bone Marrow Diseases
Myeloproliferative Disorders
Interferons
Interferon-alpha
Aspirin
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors