NCT00928707

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2009

Geographic Reach
1 country

22 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2009

Completed
24 days until next milestone

First Submitted

Initial submission to the registry

June 25, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 26, 2009

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2011

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2011

Completed
8.1 years until next milestone

Results Posted

Study results publicly available

October 31, 2019

Completed
Last Updated

October 31, 2019

Status Verified

October 1, 2019

Enrollment Period

2.1 years

First QC Date

June 25, 2009

Results QC Date

October 4, 2019

Last Update Submit

October 30, 2019

Conditions

Polycythemia Vera

Keywords

Polycythemia VeraGIVINOSTATITF2357

Outcome Measures

Primary Outcomes (1)

  • Percentage of Patients With Overall Haematological Response at Week 12.

    The percentage of patients with overall (complete or partial) response at week 12 were assessed. · Complete response: 1. HCT (Hematocrit) \< 45% without phlebotomy, and 2. platelets ≤ 400 x109/L, and 3. WBC (white blood cell) ≤ 10 x 109/L, and 4. no splenomegaly, and 5. no disease related systemic symptoms (microvascular disturbances, pruritus, headache); · Partial response: 1. HCT \< 45% without phlebotomy, or 2. fulfilment of at least 3 of the other above mentioned criteria; · No response: any response that did not satisfy the criteria set for partial response.

    At week 12 of treatment

Secondary Outcomes (3)

  • Percentage of Patients With Overall Haematological Response at Week 24 by Dose Escalation After Week 12.

    At week 24 of treatment

  • Change From Baseline of the JAK2V617F Allele Burden by Quantitative RT-PCR

    At weeks 12, 24, at "drop out visit" and at "End of Study" (EOS). EOS stays for 7 days after last drug intake if patient is withdrawn from the study before week 24.

  • Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints

    Baseline, at weeks 12 and 24

Study Arms (2)

GIVINOSTAT + MTD Hydroxyurea (HU)_1

EXPERIMENTAL

50 mg o.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy

Drug: GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea

GIVINOSTAT + MTD Hydroxyurea (HU)_2

EXPERIMENTAL

50 mg b.i.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy

Drug: GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea

Interventions

GIVINOSTAT (ITF2357) 50 mg o.d. + MTD HydroxyureaDRUG

50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy

Also known as: GIVINOSTAT (ITF2357), ONCOCARBIDE (HYDROXYUREA)
GIVINOSTAT + MTD Hydroxyurea (HU)_1
GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD HydroxyureaDRUG

50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy

Also known as: GIVINOSTAT (ITF2357), ONCOCARBIDE (HYDROXYUREA)
GIVINOSTAT + MTD Hydroxyurea (HU)_2

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 \<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.

You may not qualify if:

  • Active bacterial or mycotic infection requiring antimicrobial treatment.
  • Pregnancy or lactation.
  • A marked baseline prolongation of QT/QTc (corrected) 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 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 \<100x109/L within 14 days before enrolment.
  • Absolute neutrophil count \<1.2x109/L within 14 days before enrolment.
  • Serum creatinine \>2xULN (upper limit of normal).
  • Total serum bilirubin \>1.5xULN.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

Azienda Ospedaliero-Universitaria Policlinico Consorziale di Bari

Bari, BA, 70124, Italy

Location

Azienda Ospedaliera Santa Croce e Carle di Cuneo

Cuneo, CN, 12100, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi di Catania

Catania, CT, 95126, Italy

Location

Fondazione I. R. C. C. S. - Casa sollievo della sofferenza di San Giovanni Rotondo

San Giovanni Rotondo, FG, 71013, Italy

Location

Azienda Ospedaliero-Universitaria Careggi di Firenze

Florence, FI, 50134, Italy

Location

Azienda Ospedaliera San Gerardo di Monza

Monza, MB, 20052, Italy

Location

Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino" di Messina

Messina, ME, 98125, Italy

Location

Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello" di Palermo

Palermo, PA, 90146, Italy

Location

Azienda Unità Sanitaria Locale di Pescara, Presidio Ospedaliero "Spirito Santo"

Pescara, PE, 65124, Italy

Location

Azienda Ospedaliera Santa Maria della Misericordia di Perugia

Perugia, PG, 06156, Italy

Location

Azienda Ospedaliera Universitaria Pisana

Pisa, PI, 56126, Italy

Location

Azienda Ospedaliera Ospedale San Carlo di Potenza

Potenza, Point, 85100, Italy

Location

Fondazione I.R.C.C.S.-Policlinico San Matteo, Pavia

Pavia, PV, 27100, Italy

Location

Azienda Ospedaliera "Bianchi-Melacrino-Morelli"

Reggio Calabria, RC, 891225, Italy

Location

Azienda Ospedaliera Universitaria S. Luigi Gonzaga di Orbassano

Orbassano, TO, 10043, Italy

Location

Azienda Ospedaliero-Universitaria San Giovanni Battista("Le Molinette") di Torino

Torino, TO, 10126, Italy

Location

Ospedale Mauriziano Umberto I

Torino, TO, 10128, Italy

Location

Ospedale San Bortolo di Vicenza

Vicenza, VI, 36100, Italy

Location

Azienda Ospedaliera Ospedali Riuniti di Bergamo

Bergamo, 24100, Italy

Location

Azienda Ospedaliera Universitaria Università degli Studi di Napoli Federico II

Napoli, 80131, Italy

Location

Università "Campus Bio-Medico", Rome

Rome, 00128, Italy

Location

Policlinico Universitario Agostino Gemelli di Roma

Rome, 00168, Italy

Location

MeSH Terms

Conditions

Polycythemia Vera

Interventions

givinostatgivinostat hydrochlorideHydroxyurea

Condition Hierarchy (Ancestors)

Bone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteNeoplasmsBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesMyeloproliferative Disorders

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic Chemicals

Results Point of Contact

Title
Carlo Bianchini, MD
Organization
Italfarmaco SpA
c.bianchini@italfarmaco.com
+39 02 6443 2540

Study Officials

  • Alessandro Rambaldi, MD

    Azienda Ospedaliera Ospedali Riuniti di Bergamo

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 25, 2009

First Posted

June 26, 2009

Study Start

June 1, 2009

Primary Completion

July 1, 2011

Study Completion

October 1, 2011

Last Updated

October 31, 2019

Results First Posted

October 31, 2019

Record last verified: 2019-10

Locations

IT(22)