Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera
Condition: Polycythemia Vera
MeSH terms: Polycythemia Vera; Polycythemia
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary objective of the study was to evaluate the efficacy of Givinostat in combination
      with hydroxyurea in patients with JAK2V617F-positive Polycythemia Vera (PV) non-responders to
      the maximum tolerated dose of hydroxyurea monotherapy.

      The secondary objectives of this study were:

        -  To evaluate the safety and tolerability of Givinostat in combination with hydroxyurea in
           patients with JAK2V617Fpositive PV non-responders to the maximum tolerated dose of
           hydroxyurea monotherapy;

        -  To explore the impact in terms of efficacy and tolerability of Givinostat 50 mg dose
           escalation in patients not achieving at least a partial response at the time when the
           primary endpoint was assessed (week 12);

        -  To evaluate the molecular response (JAK2 mutated allele burden) by quantitative Real
           Time-Polymerase Chain Reaction (RT-PCR);

        -  To evaluate the reduction of the fraction of JAK2V617F positive clonogenic progenitors.
    

Detailed description: 
      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.
    

Intervention name(s): GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea; GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea
Intervention type(s): Drug; Drug
Intervention description(s): 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy; 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
Other intervention name(s): GIVINOSTAT (ITF2357); ONCOCARBIDE (HYDROXYUREA); GIVINOSTAT (ITF2357); ONCOCARBIDE (HYDROXYUREA)
Intervention MeSH terms: Hydroxyurea; Givinostat hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Polycythemia Vera; GIVINOSTAT; ITF2357