Phase 2
N=45
Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera
Polycythemia Vera
Bottom Line
View on ClinicalTrials.gov: NCT00928707 ↗Enrolled (actual)
45
Serious AEs
6.8%
Results posted
Oct 2019
Primary outcome: Primary: Percentage of Patients With Overall Haematological Response at Week 12. — 54.5; 50.0; 45.5; 50.0 percentage of particpants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea (Drug); GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Italfarmaco
- Primary completion
- Jul 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Patients With Overall Haematological Response at Week 12. |
54.5; 50.0; 45.5; 50.0 | — |
| SECONDARY Percentage of Patients With Overall Haematological Response at Week 24 by Dose Escalation After Week 12. |
63.6; 40.9; 36.4; 59.1 | — |
| SECONDARY Change From Baseline of the JAK2V617F Allele Burden by Quantitative RT-PCR |
-2.6; 0.00; -3.8; 4.6; -4.0; -9.5 | — |
| SECONDARY Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints |
27.3; 22.7; 72.7; 72.7; 0; 4.5 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Written Informed Consent.
- Age ≥18 years.
- Confirmed diagnosis of Polycythemia Vera according to the revised World Health Organization (WHO) criteria.
- JAK2V617F positivity.
- Non-response to the maximum tolerated dose of hydroxyurea monotherapy for at least 3 months.
- ECOG (Eastern Cooperative Oncology Group) performance status 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 torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
- Positive blood test for HIV (Human Immunodeficiency Virus)
- Active HBV (Hepatitis B Virus) and/or HCV (Hepatitis C Virus) infection.
- Platelets count 2xULN (upper limit of normal).
- Total serum bilirubin >1.5xULN.
- Serum aspartate aminotransferase (AST) / alanine aminotransferase (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.
Data sourced from ClinicalTrials.gov (NCT00928707). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.