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Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera (PV)

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ClinicalTrials.gov Identifier: NCT00928707
Recruitment Status : Completed
First Posted : June 26, 2009
Last Update Posted : September 18, 2012
Sponsor:
Information provided by (Responsible Party):
Italfarmaco

June 25, 2009
June 26, 2009
September 18, 2012
June 2009
July 2011   (Final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00928707 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera
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.

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Polycythemia Vera
  • Drug: GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea
    50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
    Other Names:
    • GIVINOSTAT (ITF2357)
    • ONCOCARBIDE (HYDROXYUREA)
  • Drug: GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea
    50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
    Other Names:
    • GIVINOSTAT (ITF2357)
    • ONCOCARBIDE (HYDROXYUREA)
  • Experimental: GIVINOSTAT + MTD Hydroxyurea_1
    50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
    Intervention: Drug: GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea
  • Experimental: GIVINOSTAT + MTD Hydroxyurea_2
    50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
    Intervention: Drug: GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
45
44
October 2011
July 2011   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
 
NCT00928707
DSC/08/2357/38
No
Not Provided
Not Provided
Italfarmaco
Italfarmaco
Not Provided
Principal Investigator: Alessandro Rambaldi, MD Azienda Ospedaliera Ospedali Riuniti di Bergamo
Italfarmaco
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP