Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera
Information source: Italfarmaco
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Polycythemia Vera
Intervention: GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea (Drug); GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Italfarmaco Official(s) and/or principal investigator(s):
Alessandro Rambaldi, MD, Principal Investigator, Affiliation: Azienda Ospedaliera Ospedali Riuniti di Bergamo
Overall contact:
Tiziano Oldoni, MD, Phone: +39 02 6443 2540, Email: t.oldoni@italfarmaco.com
Summary
This is a multicentre, randomized, open-label, phase II study testing GIVINOSTAT (ITF2357)
in combination with hydroxyurea in a population of patients with JAK2V617F positive
Polycythemia Vera non-responders to the maximum tolerated dose of hydroxyurea monotherapy
for at least 3 months.
Recruited patients will be randomly assigned to one of the following treatment groups:
- group A: 50 mg o. d. of oral GIVINOSTAT (ITF2357) in combination with the maximum
tolerated dose of hydroxyurea monotherapy already in use before admission to the study;
- group B: 50 mg b. i.d. of oral GIVINOSTAT (ITF2357) in combination with the maximum
tolerated dose of hydroxyurea monotherapy already in use before admission to the study.
The two groups will be balanced for number and for Centre in order to provide valuable
information on both treatment regimens.
In both groups assigned doses shall remain stable until week 12, which is when the primary
endpoint is assessed, unless specific tolerability issues arise which impose dose reduction.
After the primary endpoint assessment at week 12, one of the following treatment schedules
will be chosen case by case on the basis of the achieved clinical response and continued for
up to 12 further weeks:
- Partial or Complete Response at week 12:
- group A: continue 50 mg o. d.;
- group B: continue 50 mg b. i.d.;
- No Response at week 12:
- group A: increase to 50 mg b. i.d.;
- group B: increase to 50 mg t. i.d.. At any time during study course, if toxicity is
observed, GIVINOSTAT (ITF2357) treatment will be discontinued until recovery and then
restarted at a reduced dose level. The drug will be definitively withdrawn in case of
reappearance of toxicity even at a reduced daily dose. Overall, the treatment will last
up to a maximum of 24 cumulative weeks of drug administration.
The study will recruit subjects of both genders with an established diagnosis of JAK2V617F
positive Polycythemia Vera according to the revised WHO criteria, in need of cytoreductive
therapy, non-responders to the maximum tolerated dose of hydroxyurea monotherapy for at
least 3 months.
Clinical Details
Official title: Phase II Study of the Histone-deacetylase Inhibitor GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Patients With JAK2V617F Positive Polycythemia Vera Non-responder to Hydroxyurea Monotherapy.
Study design: Allocation: Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To evaluate the efficacy of GIVINOSTAT (ITF2357) in combination with hydroxyurea in patients with JAK2V617F positive Polycythemia Vera non-responders to the maximum tolerated dose of hydroxyurea monotherapy.
Secondary outcome: To evaluate the safety and tolerability of GIVINOSTAT-HU combination in patients with JAK2V617F positive PV NR to the MTD of HU monotherapy; to evaluate the molecular response.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Written Informed Consent.
- Age ≥18 years.
- Confirmed diagnosis of Polycythemia Vera according to the revised WHO criteria.
- JAK2V617F positivity.
- Non-response to the maximum tolerated dose of hydroxyurea monotherapy for at least 3
months.
- ECOG performance status <3.
- Use of an effective means of contraception for women of childbearing potential and
men with partners of childbearing potential.
- Willingness and capability to comply with the requirements of the study.
Exclusion Criteria:
- Active bacterial or mycotic infection requiring antimicrobial treatment.
- Pregnancy or lactation.
- A marked baseline prolongation of QT/QTc interval (e. g. repeated demonstration of a
QTc interval > 450 ms, according to Bazett's correction formula).
- Use of concomitant medications that prolong the QT/QTc interval.
- Clinically significant cardiovascular disease including:
- Uncontrolled hypertension, myocardial infarction, unstable angin,within 6 months
from study start; ;
- New York Heart Association (NYHA) Grade II or greater congestive heart failure;
- History of any cardiac arrhythmia requiring medication (irrespective of its
severity);
- A history of additional risk factors for TdP (e. g., heart failure, hypokalemia,
family history of Long QT Syndrome).
- Positive blood test for HIV.
- Active HBV and/or HCV infection.
- Platelets count <100x109/L within 14 days before enrolment.
- Absolute neutrophil count <1. 2x109/L within 14 days before enrolment.
- Serum creatinine >2xULN.
- Total serum bilirubin >1. 5xULN.
- Serum AST/ALT > 3xULN.
- History of other diseases, metabolic dysfunctions, physical examination findings, or
clinical laboratory findings giving reasonable suspicion of a disease or condition
that contraindicates use of an investigational drug or that might affect
interpretation of the results of the study or render the subject at high risk from
treatment complications.
- Interferon alpha within 14 days before enrolment.
- Anagrelide within 7 days before enrolment.
- Any other investigational drug within 28 days before enrolment.
Locations and Contacts
Tiziano Oldoni, MD, Phone: +39 02 6443 2540, Email: t.oldoni@italfarmaco.com
Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo 24100, Italy; Recruiting
Alessandro Rambaldi, MD, Phone: +39 035 269492, Email: arambaldi@ospedaliriuniti.bergamo.it
Azienda Ospedaliera Universitaria Università degli Studi di Napoli Federico II, Napoli 80131, Italy; Not yet recruiting
Vincenzo\ Martinelli, MD, Phone: +39 081 74 64 392, Email: vimartin@unina.it
Università "Campus Bio-Medico", Rome, Rome 00128, Italy; Not yet recruiting
Giuseppe Avvisati, MD, Phone: +39 06 22 54 11 049, Email: g.avvisati@unicampus.it
Policlinico Universitario Agostino Gemelli di Roma, Rome 00168, Italy; Not yet recruiting
Giuseppe Leone, MD, Phone: +39 06 30 15 41 80, Email: gleone@rm.unicatt.it
Azienda Ospedaliero-Universitaria Policlinico Consorziale di Bari, Bari, BA 70124, Italy; Recruiting
Giorgina Specchia, MD, Phone: +39 080 55 93 453, Email: g.specchia@ematba.uniba.it
Azienda Ospedaliera Santa Croce e Carle di Cuneo, Cuneo, CN 12100, Italy; Active, not recruiting
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi di Catania, Catania, CT 95126, Italy; Active, not recruiting
Fondazione I. R. C. C. S. - Casa sollievo della sofferenza di San Giovanni Rotondo, San Giovanni Rotondo, FG 71013, Italy; Not yet recruiting
Nicola Cascavilla, MD, Phone: +39 0882 41 01, Email: n.cascavilla@operapadrepio.it
Azienda Ospedaliero-Universitaria Careggi di Firenze, Florence, FI 50134, Italy; Recruiting
Alessandro M Vannucchi, MD, Phone: +39 055 79 47 688, Email: amvannucchi@unifi.it
Azienda Ospedaliera San Gerardo di Monza, Monza, MB 20052, Italy; Recruiting
Enrico M Pogliani, MD, Phone: +39 039 23 33 437, Email: enrico.pogliani@unimib.it
Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino" di Messina, Messina, ME 98125, Italy; Active, not recruiting
Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello" di Palermo, Palermo, PA 90146, Italy; Not yet recruiting
Diamante Turri, MD, Phone: +39 091 680 26 40, Email: diamanteturri@yahoo.it
Azienda Unità Sanitaria Locale di Pescara, Presidio Ospedaliero "Spirito Santo", Pescara, PE 65124, Italy; Active, not recruiting
Azienda Ospedaliera Santa Maria della Misericordia di Perugia, Perugia, PG 06156, Italy; Not yet recruiting
Brunangelo Falini, MD, Phone: +39 075 57 83 190, Email: faliniem@unipg.it
Azienda Ospedaliera Universitaria Pisana, Pisa, PI 56126, Italy; Active, not recruiting
Azienda Ospedaliera Ospedale San Carlo di Potenza, Potenza, PT 85100, Italy; Not yet recruiting
Attilio Olivieri, MD, Phone: +39 0971 61 36 60, Email: attilio.olivieri@ospedalesancarlo.it
Fondazione I.R.C.C.S.-Policlinico San Matteo, Pavia, Pavia, PV 27100, Italy; Recruiting
Giovanni Barosi, MD, Phone: +39 0382 50 36 36, Email: barosig@smatteo.pv.it
Azienda Ospedaliera "Bianchi-Melacrino-Morelli", Reggio di Calabria, RC 891225, Italy; Recruiting
Francesco Nobile, MD, Phone: +39 0965 39 72 23, Email: nobile.franc@gmail.com
Azienda Ospedaliera Universitaria S. Luigi Gonzaga di Orbassano, Orbassano, TO 10043, Italy; Not yet recruiting
Giuseppe Saglio, MD, Phone: +39 011 90 26 305, Email: ematologia@sanluigi.piemonte.it
Ospedale Mauriziano Umberto I, Torino, TO 10128, Italy; Not yet recruiting
Corrado Tarella, MD, Phone: +39 011 508 29 49, Email: corrado.tarella@unito.it
Azienda Ospedaliero-Universitaria San Giovanni Battista("Le Molinette") di Torino, Torino, TO 10126, Italy; Not yet recruiting
Umberto Vitolo, MD, Phone: +39 011 63 35 550, Email: uvitolo@molinette.piemonte.it
Ospedale San Bortolo di Vicenza, Vicenza, VI 36100, Italy; Recruiting
Francesco Rodeghiero, MD, Phone: +39 0444 75 36 26, Email: rodeghiero@hemato.ven.it
Additional Information
Starting date: June 2009
Last updated: July 26, 2010
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