Myeloproliferative DiseasesPhase 2NCT00606307
Phase IIA Study of the HDAC Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases
A Phase 2 study testing ITF2357 in people with Myeloproliferative Diseases, run by Italfarmaco at 2 sites in Italy.
Trial summary
Primary Objective: To evaluate efficacy and safety of ITF2357 in the treatment of patients with JAK2V617F positive myeloproliferative diseases [Polycythemia Vera (PV), Essential Thrombocytosis (ET), Myelofibrosis (MF)]. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloproliferative Diseases
- What is being tested?
- ITF2357
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesItaly
- Study dates
- Dec 2007to Dec 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent Form
- Male or female, age ≥ 18 years
- Confirmed diagnosis of PV/ET/MF according to the revised World Health Organisation criteria
- JAK-2 V617F positivity
- In need of cytoreductive therapy when hydroxyurea is not indicated (e.g. young patients) or when refractoriness to the drug is documented
Who cannot join
- Active bacterial or fungal infection requiring antimicrobial treatment on Day 1
- Patients of childbearing potential without a negative pregnancy test prior to initiation of the study drug
- Pregnancy or lactation
- A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett's correction formula - see appendix G for the formula)
- The use of concomitant medications that prolong the QT/QTc interval (see appendix F for full list)
- Concomitant acute coronary syndromes; uncontrolled hypertension
Show all 24Show fewer
- 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 (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- Active Epstein Barr Virus (EBV) infection (i.e. positive serology IgM)
- Known HIV infection
- Active hepatitis B and/or C infection
- History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding 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
- Eastern Cooperative Oncology Group (ECOG) performance status 3 or greater
- Platelets count <100x109/L within 14 days before enrolment
- Absolute neutrophil count <1.2x109/L within 14 days before enrolment
- Percentage of blast cells in peripheral blood >10% within 14 days before enrolment
- Serum creatinine >2xULN (Upper limit of normal)
- Total serum bilirubin >1.5xULN
- Serum AST (aspartate aminotransferase) / ALT (alanine aminotransferase) > 3xULN
- Interferon alpha within 14 days before enrolment
- Hydroxyurea within 14 days before enrolment
- Anagrelide within 7 days before enrolment
- Any other investigational drug within 28 days before enrolment
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Ospedali riuniti
Bergamo, 24158
IRCCS - Pol. San Matteo
Pavia, 27100
About this study
Official title: A Phase IIA Study of the Histone-deacetylase Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases
Primary Objective:
To evaluate efficacy and safety of ITF2357 in the treatment of patients with JAK2V617F positive myeloproliferative diseases [Polycythemia Vera (PV), Essential Thrombocytosis (ET), Myelofibrosis (MF)]. Efficacy was evaluated by ad hoc haematological and clinical criteria for PV and ET, and by internationally established response criteria (EUMNET criteria) for MF. Safety was evaluated by number of subjects experiencing an Adverse Event (AE), type, frequency, severity, timing and relatedness of AEs, including changes in vital signs and clinical laboratory results.
Read more
Secondary Objective:
To evaluate the JAK2 mutated allele burden by quantitative Real-Time Polymerase Chain Reaction (qRTPCR).
Read the detailed description
This is a non-randomized, open-label, Phase IIA pilot study testing efficacy and safety of ITF2357 in a population of patients with JAK2V617F positive myeloproliferative diseases. All recruited patients received an initial dose of 50 mg b.i.d. of ITF2357 that was subsequently escalated to 50 mg t.i.d. in case of lack of significant toxicity. Treatment lasted up to a maximum of 24 cumulative weeks of drug administration. The study was carried out in Italy. Enrolled patients were subjects of both genders, with an established diagnosis of polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) according to the revised WHO criteria.
- Conditions
- Myeloproliferative Diseases
- Being tested
- ITF2357
- Keywords
- polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF)
- Medical subject headings
- Polycythemia Vera, Thrombocythemia, Essential, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ITF2357Drug
Also called Givinostat
50 mg b.i.d. PO every day. More precisely, ITF2357 was supplied as 50 mg hard gelatine capsules for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| ITF2357 | Experimental | Initial dose of 50 mg b.i.d. that was subsequently escalated to 50 mg t.i.d in case of lack of significant toxicity. Receives: Drug: ITF2357 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Objective Responses (Complete, Major, Moderate or Minor Responses), in Terms of Best Overall Response
Patients with Objective Response were defined as those patients achieving a complete, major, moderate or minor (only for Myelofibrosis patients) response during the experimental treatment course.
The "best response" is reported hereunder by intensity of response.
Measured: Every single week from week 1 to week 24 of treatment
Secondary outcomes (2)
Change in JAK2 Mutated Allele Burden
This outcome was assessed by quantitative real time Polymerase Chain Reaction (RT PCR).
At each time point, the number of patients is the following:
Screening: N=29 Week 12: N=20 Week 24: N=18 EOT: N=24. End of treatment corresponds to the last visit performed before treatment discontinuation.
Measured: At screening, at week 12, at week 24, at the end of treatment (EOT) visit
Number of Subject Experiencing an Adverse Event
An adverse event (AE) is any untoward occurrence in a patient or clinical investigation subject administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
The adverse events must to be followed to the end of study (28 days after the last study drug intake).
A serious AE (SAE) is defined as an untoward (unfavourable) medical occurrence that at any dose results in death, or is life-threatening or requires inpatient hospitalisation or prolongation of existing hospitalisation, or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.
Measured: At weekly visits (Days 8, 15, 22, 36, 43, 50, 64, 71, 78, 99, 127, 155); At monthly visits (Days 29, 57, 85 113, 141,169); at end of treatment visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2008 (estimated)
- Study startDec 2007
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myeloproliferative DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italfarmaco
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- tiziano oldoni, MD, Study director, ItalfarmacoAlessandro Rambaldi, MD, Principal investigator, A.O. Ospedale Papa Giovanni XXIII
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00606307
- Sponsor's protocol ID
- DSC/07/2357/28
- Status last verified
- Nov 2019
- First submitted
- 21 Jan 2008
- Last updated
- 3 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIA Study of the Histone-deacetylase Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases
- ClinicalTrials.gov ID
- NCT00606307
- Acronym / sponsor ID
- DSC/07/2357/28
- Conditions
- Myeloproliferative Diseases
- Keywords
- polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- ItalfarmacoIndustry (pharma, biotech, devices)
- Study start
- Dec 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 1 Feb 2008 (estimated)
- Results
- Posted 3 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To evaluate efficacy and safety of ITF2357 in the treatment of patients with JAK2V617F positive myeloproliferative diseases [Polycythemia Vera (PV), Essential Thrombocytosis (ET), Myelofibrosis (MF)]. Efficacy was evaluated by ad hoc haematological and clinical criteria for PV and ET, and by internationally established response criteria (EUMNET criteria) for MF. Safety was evaluated by number of subjects experiencing an Adverse Event (AE), type, frequency, severity, timing and relatedness of AEs, including changes in vital signs and clinical laboratory results.
Secondary Objective:
To evaluate the JAK2 mutated allele burden by quantitative Real-Time Polymerase Chain Reaction (qRTPCR).
Detailed description
This is a non-randomized, open-label, Phase IIA pilot study testing efficacy and safety of ITF2357 in a population of patients with JAK2V617F positive myeloproliferative diseases. All recruited patients received an initial dose of 50 mg b.i.d. of ITF2357 that was subsequently escalated to 50 mg t.i.d. in case of lack of significant toxicity. Treatment lasted up to a maximum of 24 cumulative weeks of drug administration. The study was carried out in Italy. Enrolled patients were subjects of both genders, with an established diagnosis of polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) according to the revised WHO criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ITF2357 | Experimental | Drug: ITF2357Initial dose of 50 mg b.i.d. that was subsequently escalated to 50 mg t.i.d in case of lack of significant toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Signed Informed Consent Form
- Male or female, age ≥ 18 years
- Confirmed diagnosis of PV/ET/MF according to the revised World Health Organisation criteria
- JAK-2 V617F positivity
- In need of cytoreductive therapy when hydroxyurea is not indicated (e.g. young patients) or when refractoriness to the drug is documented
Key exclusion criteria (24 listed)
- Active bacterial or fungal infection requiring antimicrobial treatment on Day 1
- Patients of childbearing potential without a negative pregnancy test prior to initiation of the study drug
- Pregnancy or lactation
- A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett's correction formula - see appendix G for the formula)
- The use of concomitant medications that prolong the QT/QTc interval (see appendix F for full list)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ITF2357Also: Givinostat50 mg b.i.d. PO every day. More precisely, ITF2357 was supplied as 50 mg hard gelatine capsules for oral administration. | Drug | ITF2357 |
Primary outcome
Number of Patients With Objective Responses (Complete, Major, Moderate or Minor Responses), in Terms of Best Overall Response
Time frame: Every single week from week 1 to week 24 of treatment
Patients with Objective Response were defined as those patients achieving a complete, major, moderate or minor (only for Myelofibrosis patients) response during the experimental treatment course. The "best response" is reported hereunder by intensity of response.
2 secondary outcomes
Change in JAK2 Mutated Allele Burden
Time frame: At screening, at week 12, at week 24, at the end of treatment (EOT) visit
Number of Subject Experiencing an Adverse Event
Time frame: At weekly visits (Days 8, 15, 22, 36, 43, 50, 64, 71, 78, 99, 127, 155); At monthly visits (Days 29, 57, 85 113, 141,169); at end of treatment visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
tiziano oldoni, MD study director
Italfarmaco
Alessandro Rambaldi, MD principal investigator
A.O. Ospedale Papa Giovanni XXIII
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ITF2357 in people with Myeloproliferative Diseases, run by Italfarmaco at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Objective Responses (Complete, Major, Moderate or Minor Responses), in Terms of Best Overall Response (time frame: Every single week from week 1 to week 24 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2019.