Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms

NCT01761968 | Active Not Recruiting Phase 2

• 2 other identifiers: DSC/11/2357/442012-003499-37
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 15

Brief Summary

This is a multicenter, open label, long-term study testing the long-term safety, tolerability and efficacy of givinostat in patients with Polycythemia Vera, Essential Thrombocythemia, primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis following core protocols in chronic myeloproliferative neoplasms and/or patient-named compassionate use program (if regulated/allowed by the local regulations, e.g. for Italy D.M. 8/5/2003 "Uso terapeutico di medicinale sottoposto a sperimentazione clinica" published on G.U. n. 173 of 28 July 2003, and the following amendments). Patients will continue at their last tolerable dose and treatment schedule of givinostat monotherapy. If patients previously received givinostat in combination with other drugs during a core protocol or a compassionate use program (if regulated/allowed by the local regulations, e.g. for Italy D.M. 8/5/2003 "Uso terapeutico di medicinale sottoposto a sperimentazione clinica" published on G.U. n. 173 of 28 July 2003, and the following amendments), they will be treated at the last tolerable dose of the combination. Assessment of safety and efficacy will be performed at each quarterly visit and each visit will also include laboratory tests and ECG examination. During the visits the clinical benefit will be assessed by Investigator according to the revised European LeukemiaNet response criteria (for PV and ET) and EUMNET response criteria (for MF). The dose of Givinostat will be modified for protocol specified toxicities. The treatment may continue up to Marketing Authorization of givinostat, currently planned in the next 5 years (note: only for Germany, this long-term study is initially limited up to 2 years of treatment). Patients may discontinue study treatment at any time and remain on study therapy as long as they derive clinical benefit. Safety will be monitored at each visit throughout the entire duration of the study. In case the approved label will not cover the whole study population, givinostat will be provided by the Sponsor to those patients not fulfilling the criteria for the approved label of the drug that are still deriving benefit from givinostat at the time of its commercial availability.

Conditions

Chronic Myeloproliferative Neoplasms

Keywords

chronic myeloproliferative neoplasms; Polycythemia Vera; Essential Thrombocythemia; Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis; Givinostat

Outcome Measures

Primary Outcomes (1)

• Long-term safety and efficacy

  To obtain information on the long-term safety and tolerability of givinostat in patients with chronic myeloproliferative neoplasms following core protocols or compassionate use program: * Number of patients experiencing adverse events; * Type, incidence, and severity of treatment-related adverse events. To determine the long term efficacy of givinostat in patients with chronic myeloproliferative neoplasms following core protocols or compassionate use program: * For Polycythemia Vera and Essential Thrombocythemia, Complete response and partial response rate according to the revised clinico-haematological European LeukemiaNet response criteria; * For Myelofibrosis, complete response, major response, moderate response and minor response rate according to European Myelofibrosis Network response criteria. Note that these assessment will be repeated periodically (each 3 months) during the study. In fact, the treatment will continue up to Marketing Authorisation of givinostat.

  3 months

Other Outcomes (5)

• Clinical exploratory endpoint

  1 year

• Molecular exploratory endpoint

  1 year

• Biomolecular exploratory endpoint

  1 year

Study Arms (1)

givinostat

EXPERIMENTAL

Patients will continue at their last tolerable dose and treatment schedule of givinostat monotherapy. Givinostat is a histone-deacetylases inhibitor. The product will be supplied as hard gelatine capsules for oral administration at the strength of 50 mg, 75 mg and/or 100 mg each. If patients previously received givinostat in combination with other drugs during a core protocol or a compassionate use program, they will be treated at their last tolerable dose of this combination.

Drug: givinostat

Interventions

givinostat DRUG

Patients will continue at their last tolerable dose and treatment schedule of givinostat monotherapy. Givinostat is a histone-deacetylases inhibitor. The product will be supplied as hard gelatine capsules for oral administration at the strength of 50 mg, 75 mg and/or 100 mg each. If patients previously received givinostat in combination with other drugs during a core protocol or a compassionate use program, they will be treated at their last tolerable dose of this combination.

Also known as: givinostat (ITF2357)

givinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have completed givinostat treatment on at least one core study in chronic myeloproliferative neoplasms, or patients must be participating in a compassionate use program with givinostat AND Patients must have tolerated previous givinostat treatment and achieved a clinical benefit at the end of core protocols or compassionate use program with givinostat, assessed by the Investigator according to the revised clinico-haematological ELN response criteria (for PV and ET) and EUMNET response criteria (for MF);
• Patients must be able to provide informed consent and be willing to sign an informed consent form;
• Adult patients (age ≥ 18 years) of both genders with established diagnosis of chronic myeloproliferative neoplasms according to the revised WHO criteria;
• Patients must have an Eastern Cooperative Oncology Group performance status \< 3 at baseline;
• Acceptable organ function within 7 days of initiating study drug;
• 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:

• Pregnancy or nursing (lactating) women, where pregnancy is defined as the state of a female after conception, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test (i.e. \> 5 mIU/mL) and until the termination of gestation;
• A clinically significant corrected QT interval prolongation at baseline;
• Use of concomitant medications known to prolong the corrected QT interval;
• Clinically significant cardiovascular disease including:
• Uncontrolled hypertension, myocardial infarction, unstable angina at screening;
• New York Heart Association 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 Point;
• Active virus infection including human HIV, HBV and HCV;
• Platelets count \< 100 x109/L within 14 days before enrolment (i.e. the receipt of the Patient ID);
• Absolute neutrophil count \< 1.2 x109/L within 14 days before enrolment (i.e. the receipt of the Patient ID);
• Total serum bilirubin \> 1.5 1.5 x ULN except in case of Gilbert's disease or pattern consistent with Gilbert's disease;
• Serum Aspartate aminotransferase/Alanine aminotransferase (AST/ALT) \> 3 times the upper normal limit;
• Uncontrolled hypertriglyceridemia at baseline, i.e. triglycerides ˃ 1.5 x ULN in fasting state.
• History and/or presence 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 patient at high risk from treatment complications or significantly alter the absorption of the study drug;

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (15)

Charite Research Organization GmbH

Berlin, 10117, Germany

Location

Universitaetsklinikum Freiburg, Innere Medizin I - Haematologie und Onkologie

Freiburg im Breisgau, 79106, Germany

Location

Azienda Ospedaliero-Universitaria Policlinico Consorziale, Bari

Bari, BA, 70124, Italy

Location

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico di Bari

Bari, BA, 70125, Italy

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, BG, 24127, Italy

Location

Azienda Ospedaliero-Universitaria Careggi, Florence

Florence, FI, 50134, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico UOS Oncoematologia anziano

Milan, MI, 20122, Italy

Location

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

Pescara, PE, 65124, 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, 89124, Italy

Location

Ospedale San Bortolo, Vicenza

Vicenza, VI, 36100, Italy

Location

Azienda Ospedaliera Universitaria Università degli Studi "Federico II", Naple

Naples, 80131, Italy

Location

Università "Campus Bio-Medico", Rome

Rome, 00128, Italy

Location

Belfast City Hospital

Belfast, BT9 7BL, United Kingdom

Location

Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis

Interventions

givinostat; givinostat hydrochloride

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Study Officials

• Alessandro Rambaldi, MD

  Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2012
• First Posted: January 7, 2013
• Study Start: March 1, 2013
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 30, 2025

Record last verified: 2025-04

Locations

GB (2); IT (11); DE (2)