Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera (PV)
This study has been completed.
Sponsor:
Italfarmaco
Information provided by (Responsible Party):
Italfarmaco
ClinicalTrials.gov Identifier:
NCT00928707
First received: June 25, 2009
Last updated: September 17, 2012
Last verified: September 2012
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Purpose
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 The drug will be definitively withdrawn in case of reappearance of toxicity even at a reduced daily dose.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.
| Condition | Intervention | Phase |
|---|---|---|
|
Polycythemia Vera |
Drug: GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea Drug: GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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. |
Resource links provided by NLM:
Genetics Home Reference related topics:
polycythemia vera
Drug Information available for:
Hydroxyurea
U.S. FDA Resources
Further study details as provided by Italfarmaco:
Primary Outcome Measures:
- 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. [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 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. [ Time Frame: after 24 weeks of treatment ] [ Designated as safety issue: Yes ]
| Enrollment: | 45 |
| Study Start Date: | June 2009 |
| Study Completion Date: | October 2011 |
| Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: GIVINOSTAT + MTD Hydroxyurea_1
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
|
Drug: GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
Other Names:
|
|
Experimental: GIVINOSTAT + MTD Hydroxyurea_2
50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
|
Drug: GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea
50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
Other Names:
|
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00928707
Locations
| Italy | |
| Azienda Ospedaliero-Universitaria Policlinico Consorziale di Bari | |
| Bari, BA, Italy, 70124 | |
| Azienda Ospedaliera Santa Croce e Carle di Cuneo | |
| Cuneo, CN, Italy, 12100 | |
| Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi di Catania | |
| Catania, CT, Italy, 95126 | |
| Fondazione I. R. C. C. S. - Casa sollievo della sofferenza di San Giovanni Rotondo | |
| San Giovanni Rotondo, FG, Italy, 71013 | |
| Azienda Ospedaliero-Universitaria Careggi di Firenze | |
| Florence, FI, Italy, 50134 | |
| Azienda Ospedaliera San Gerardo di Monza | |
| Monza, MB, Italy, 20052 | |
| Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino" di Messina | |
| Messina, ME, Italy, 98125 | |
| Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello" di Palermo | |
| Palermo, PA, Italy, 90146 | |
| Azienda Unità Sanitaria Locale di Pescara, Presidio Ospedaliero "Spirito Santo" | |
| Pescara, PE, Italy, 65124 | |
| Azienda Ospedaliera Santa Maria della Misericordia di Perugia | |
| Perugia, PG, Italy, 06156 | |
| Azienda Ospedaliera Universitaria Pisana | |
| Pisa, PI, Italy, 56126 | |
| Azienda Ospedaliera Ospedale San Carlo di Potenza | |
| Potenza, PT, Italy, 85100 | |
| Fondazione I.R.C.C.S.-Policlinico San Matteo, Pavia | |
| Pavia, PV, Italy, 27100 | |
| Azienda Ospedaliera "Bianchi-Melacrino-Morelli" | |
| Reggio di Calabria, RC, Italy, 891225 | |
| Azienda Ospedaliera Universitaria S. Luigi Gonzaga di Orbassano | |
| Orbassano, TO, Italy, 10043 | |
| Ospedale Mauriziano Umberto I | |
| Torino, TO, Italy, 10128 | |
| Azienda Ospedaliero-Universitaria San Giovanni Battista("Le Molinette") di Torino | |
| Torino, TO, Italy, 10126 | |
| Ospedale San Bortolo di Vicenza | |
| Vicenza, VI, Italy, 36100 | |
| Azienda Ospedaliera Ospedali Riuniti di Bergamo | |
| Bergamo, Italy, 24100 | |
| Azienda Ospedaliera Universitaria Università degli Studi di Napoli Federico II | |
| Napoli, Italy, 80131 | |
| Università "Campus Bio-Medico", Rome | |
| Rome, Italy, 00128 | |
| Policlinico Universitario Agostino Gemelli di Roma | |
| Rome, Italy, 00168 | |
Sponsors and Collaborators
Italfarmaco
Investigators
| Principal Investigator: | Alessandro Rambaldi, MD | Azienda Ospedaliera Ospedali Riuniti di Bergamo |
More Information
No publications provided
| Responsible Party: | Italfarmaco |
| ClinicalTrials.gov Identifier: | NCT00928707 History of Changes |
| Other Study ID Numbers: | DSC/08/2357/38 |
| Study First Received: | June 25, 2009 |
| Last Updated: | September 17, 2012 |
| Health Authority: | Italy: Ministry of Health |
Keywords provided by Italfarmaco:
|
Polycythemia Vera GIVINOSTAT ITF2357 |
Additional relevant MeSH terms:
|
Polycythemia Polycythemia Vera Hematologic Diseases Myeloproliferative Disorders Bone Marrow Diseases Hydroxyurea Histone Deacetylase Inhibitors Antineoplastic Agents |
Therapeutic Uses Pharmacologic Actions Antisickling Agents Hematologic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors |
ClinicalTrials.gov processed this record on May 21, 2013