Conditions: Polycythemia Vera
Keywords: Polycythemia Vera GIVINOSTAT ITF2357
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 45
Healthy volunteers: no

Brief 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.

Arms:
arm 1: 50 mg o.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy arm 2: 50 mg b.i.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy

Interventions: intervention 1: GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea intervention 2: GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea
Intervention descriptions: intervention 1: 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy intervention 2: 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy

Protocol document: