Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms
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ClinicalTrials.gov Identifier: NCT01761968 |
Recruitment Status :
Active, not recruiting
First Posted : January 7, 2013
Last Update Posted : June 15, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Chronic Myeloproliferative Neoplasms | Drug: givinostat | Phase 2 |

Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 90 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Long-term Study Evaluating the Effect of Givinostat in Patients With JAK2V617F Positive Chronic Myeloproliferative Neoplasms |
Study Start Date : | March 2013 |
Estimated Primary Completion Date : | June 2025 |
Estimated Study Completion Date : | December 2025 |

Arm | Intervention/treatment |
---|---|
Experimental: givinostat
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
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. Other Name: givinostat (ITF2357) |
- Long-term safety and efficacy [ Time Frame: 3 months ]
To obtain information on the long-term efficacy 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 safety and tolerability 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.
- Clinical exploratory endpoint [ Time Frame: 1 year ]
To evaluate the effect of givinostat on each single response parameter according to the revised European LeukemiaNet (for Polycythemia Vera and Essential Thrombocythemia) and European European Myelofibrosis Network response criteria (for Myelofibrosis).
Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of givinostat.
- Molecular exploratory endpoint [ Time Frame: 1 year ]
To evaluate the molecular response (i.e. reduction of the allele burden of the mutated Janus Kinase 2 in the position V617F).
Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of givinostat.
- Biomolecular exploratory endpoint [ Time Frame: 1 year ]
To identify potential other markers predictive of clinical benefit of givinostat (e.g. potential pharmacodynamic markers).
Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of givinostat.
- Progression Free Survival [ Time Frame: 1 year ]To evaluate the disease parameters related to disease evolution
- Thrombotic Rate [ Time Frame: 1 year ]To evaluate thrombotic rate

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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;
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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;
- Serum Cystatin C > 2 x ULN for two subsequent evaluations (i.e. if the value of serum Cystatin C is >2 x ULN, the test will be repeated once, and if the value is again > 2 x ULN, this becomes an exclusioncriterion);
- 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;
- Any investigational drug other than givinostat within 28 days before enrolment. Notably, the use of such medications within 28 days or 6 half-lives - whichever is longer - prior to the first dose of study drugs (i.e. Day 1) and during the study through all the study conduct (including any safety follow-up [FU] visit) is prohibited;
- Use of concomitant medications known to inhibit Pgp;
- Patients with known hypersensitivity to the components of potential study therapy.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01761968
Germany | |
Charite Research Organization GmbH | |
Berlin, Germany, 10117 | |
Universitaetsklinikum Freiburg, Innere Medizin I - Haematologie und Onkologie | |
Freiburg, Germany, 79106 | |
Italy | |
Azienda Ospedaliero-Universitaria Policlinico Consorziale, Bari | |
Bari, BA, Italy, 70124 | |
Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico di Bari | |
Bari, BA, Italy, 70125 | |
Azienda Ospedaliera Papa Giovanni XXIII | |
Bergamo, BG, Italy, 24127 | |
Azienda Ospedaliero-Universitaria Careggi, Florence | |
Florence, FI, Italy, 50134 | |
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico UOS Oncoematologia anziano | |
Milan, MI, Italy, 20122 | |
Azienda Unità Sanitaria Locale - Presidio Ospedaliero "Spirito Santo", Pescara | |
Pescara, PE, Italy, 65124 | |
Fondazione I.R.C.C.S.-Policlinico San Matteo, Pavia | |
Pavia, PV, Italy, 27100 | |
Azienda Ospedaliera "Bianchi-Melacrino-Morelli" | |
Reggio Calabria, RC, Italy, 89124 | |
Ospedale San Bortolo, Vicenza | |
Vicenza, VI, Italy, 36100 | |
Azienda Ospedaliera Universitaria Università degli Studi "Federico II", Naple | |
Naples, Italy, 80131 | |
Università "Campus Bio-Medico", Rome | |
Rome, Italy, 00128 | |
United Kingdom | |
Belfast City Hospital | |
Belfast, United Kingdom, BT9 7BL | |
Royal Cornwall Hospital | |
Truro, United Kingdom, TR1 3LJ |
Principal Investigator: | Alessandro Rambaldi, MD | Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy |
Responsible Party: | Italfarmaco |
ClinicalTrials.gov Identifier: | NCT01761968 |
Other Study ID Numbers: |
DSC/11/2357/44 2012-003499-37 ( EudraCT Number ) |
First Posted: | January 7, 2013 Key Record Dates |
Last Update Posted: | June 15, 2021 |
Last Verified: | April 2021 |
chronic myeloproliferative neoplasms Polycythemia Vera Essential Thrombocythemia Primary Myelofibrosis |
Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis Givinostat |
Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
Givinostat hydrochloride Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |