Idiopathic MyelofibrosisPhase 1NCT01433445
Panobinostat and Ruxolitinib in Primary Myelofibrosis, Post-polycythemia Vera-myelofibrosis or Post-essential Thrombocythemia-myelofibrosis
A Phase 1 study testing panobinostat and ruxolitinib in people with Idiopathic Myelofibrosis and Post Essential Thrombocythemia Myelofibrosis, run by Novartis Pharmaceuticals at 10 sites in 5 countries.
Trial summary
This study will assess safety as well as establish a Recommended Phase II dose of the combination of panobinostat and ruxolitinib in patients with or without the JAK2V617F mutation who have been diagnosed with primary myelofibrosis (PMF), Post Essential Thrombocythemia Myelofibrosis (PET MF), or Post-Polycythemia Vera… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Post Polycythemia-Vera Myelofibrosis
- What is being tested?
- panobinostat and ruxolitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 10 sitesin 5 countries
- Study dates
- 1 Nov 2011to 22 Jun 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Diagnosis of myelofibrosis, either PMF, PPV or PET MF
- Palpable splenomegaly ≥ 5cm
- May have been previously treated with either panobinostat or ruxolitinib (unless discontinued for clinically relevant toxicities)
- Acceptable lab ranges for all organ systems
- Specifically: Platelet count > 100,000 not reached with the aide of transfusions
- Blast count < 10% at screening
- ECOG ≤ 2
- Must be able to discontinue all drugs being used to treat MF at least 7 days prior to starting study drug
Who cannot join
- Active malignancy
- Clinically significant heart disease
- Splenic irradiation within 12 months of starting study drug
- Need for ongoing systemic anticoagulation with the exception of Aspirin < 150mg/day or Low Molecular Weight Heparin
- History of platelet dysfunction or bleeding disorder in the 6 months prior to screening
- Patient is at risk for spontaneous bleeding
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- Willing and/or eligible for stem-cell transplantation
- Impairment of gastro-intestinal function that may impact the absorption of study treatment
- Unwilling to use highly effective methods of contraception during dosing and for 13 weeks (female participants) or for 6 months (male participants and their female partners) after stopping study treatment
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
Italy3 sites
Novartis Investigative Site
Florence, FI, 50134
Novartis Investigative Site
Reggio Calabria, RC, 89124
Novartis Investigative Site
Varese, VA, 21100
France2 sites
Novartis Investigative Site
Paris, 75010
Novartis Investigative Site
Villejuif, 94800
Germany2 sites
Novartis Investigative Site
Magdeburg, 39120
Novartis Investigative Site
Mainz, 55131
Ireland2 sites
Novartis Investigative Site
Dublin, DUBLIN 8
Novartis Investigative Site
Galway
About this study
Official title: A Phase 1b, Open-label, Multi-center, Single Arm, Dose Finding Study to Assess Safety and Pharmacokinetics of the Oral Combination of Panobinostat and Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-polycythemia Vera-myelofibrosis (PPV-MF) or Post-essential Thrombocythemia-myelofibrosis (PET-MF)
This study will assess safety as well as establish a Recommended Phase II dose of the combination of panobinostat and ruxolitinib in patients with or without the JAK2V617F mutation who have been diagnosed with primary myelofibrosis (PMF), Post Essential Thrombocythemia Myelofibrosis (PET MF), or Post-Polycythemia Vera Myelofibrosis (PPV MF).
Read the detailed description
In 2011 the treatment goals for MF focused on symptom-orientated palliation and quality of life. Both ruxolitinib and panobinostat, as single agents, had shown significant improvement in both of those treatment goals and ruxolitinib had also shown greater reductions in splenomegaly compared to the standard of care at that time. To further the benefit seen with ruxolitinib in MF patients, panobinostat was added to the treatment regimen to act synergistically in the blockade of the dysregulated pathway driving this disease.
The study was conducted in 2 phases - an escalation phase and an expansion phase.
Escalation phase: the study utilised the Bayesian Logistic Regression Model (BLRM), incorporating escalation with overdose control (EWOC), which is a well established method for dose escalation in oncology trials. Following this process, successive cohorts of 3 newly enrolled patients received increasing doses of ruxolitinib and panobinostat until the maximum tolerated dose (MTD) or recommended phase II dose (RPIID) was determined. Once the MTD and/or RPIID were suspected in a minimum of 3 patients, additional patients were enrolled to the same cohort level to reach a minimum of 9 evaluable patients. The process also included safety, PK/PD assessments and estimates of efficacy based on measures of splenic reduction at each dose level.
Expansion: following the determination of the MTD and/or RPIID, a dose expansion phase was conducted at that dose to further define the safety and tolerability of the combination. At least 13, and no more than 23, additional patients were to be enrolled into the expansion phase.
- Conditions
- Idiopathic Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Post Polycythemia-Vera Myelofibrosis
- Being tested
- panobinostat, ruxolitinib
- Keywords
- Myelofibrosis, Panobinostat, LBH589, Ruxolitinib, MF, PMF, PPV, PPV-MF, PET, PET-MF, JAK2, DACi
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
panobinostatDrug
Also called LBH589
Given 3 times a week, every other week in 28-day cycles.
ruxolitinibDrug
Also called INC424
Given twice daily in 28-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects will be treated with ruxolitinib 5 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle Receives: Drug: panobinostat; Drug: ruxolitinib |
| Cohort 2 | Experimental | Subjects will be treated with ruxolitinib 10 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle Receives: Drug: panobinostat; Drug: ruxolitinib |
| Cohort 3 | Experimental | Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle Receives: Drug: panobinostat; Drug: ruxolitinib |
| Cohort 4 | Experimental | Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 15 mg three times per week (TIW) every other week (QOW) on a 28 day cycle Receives: Drug: panobinostat; Drug: ruxolitinib |
| Cohort 5 | Experimental | Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 20 mg three times per week (TIW) every other week (QOW) on a 28 day cycle Receives: Drug: panobinostat; Drug: ruxolitinib |
| Cohort 6/6+ | Experimental | Subjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 25 mg three times per week (TIW) every other week (QOW) on a 28 day cycle Receives: Drug: panobinostat; Drug: ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose limiting toxicities at the different dose levels
Measured: Cycle 1 (a cycle = 28 days)
Secondary outcomes (4)
Rate of adverse events, serious adverse events, notable laboratory, vital signs and ECG results by dose level
Measured: From screening until safety follow up visit (30 days after last treatment), approx. 8.5 years
AUC of ruxolitinib and panobinostat at various dose levels
Area under the plasma concentration versus time curve
Measured: Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7
Cmax of ruxolitinib and panobinostat at various dose levels
Cmax is the Peak Plasma Concentration
Measured: Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7
Tmax of ruxolitinib and panobinostat at various dose levels
Tmax: The time of maximum observed concentration sampled during a dosing interval.
Measured: Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2011 (estimated)
- Study start1 Nov 2011
- Primary completion22 Jun 2020
- Study completion22 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic MyelofibrosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01433445
- Sponsor's protocol ID
- CLBH589X2106
- Other IDs
- 2011-000861-10
- Status last verified
- Jun 2021
- First submitted
- 27 Jun 2011
- Last updated
- 25 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-label, Multi-center, Single Arm, Dose Finding Study to Assess Safety and Pharmacokinetics of the Oral Combination of Panobinostat and Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-polycythemia Vera-myelofibrosis (PPV-MF) or Post-essential Thrombocythemia-myelofibrosis (PET-MF)
- ClinicalTrials.gov ID
- NCT01433445
- Acronym / sponsor ID
- CLBH589X2106
- Conditions
- Idiopathic Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Post Polycythemia-Vera Myelofibrosis
- Keywords
- Myelofibrosis, Panobinostat, LBH589, Ruxolitinib, MF, PMF, PPV, PPV-MF
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2011 (actual)
- Primary completion
- 22 Jun 2020 (actual)
- Study completion
- 22 Jun 2020 (actual)
- First posted
- 14 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess safety as well as establish a Recommended Phase II dose of the combination of panobinostat and ruxolitinib in patients with or without the JAK2V617F mutation who have been diagnosed with primary myelofibrosis (PMF), Post Essential Thrombocythemia Myelofibrosis (PET MF), or Post-Polycythemia Vera Myelofibrosis (PPV MF).
Detailed description
In 2011 the treatment goals for MF focused on symptom-orientated palliation and quality of life. Both ruxolitinib and panobinostat, as single agents, had shown significant improvement in both of those treatment goals and ruxolitinib had also shown greater reductions in splenomegaly compared to the standard of care at that time. To further the benefit seen with ruxolitinib in MF patients, panobinostat was added to the treatment regimen to act synergistically in the blockade of the dysregulated pathway driving this disease.
The study was conducted in 2 phases - an escalation phase and an expansion phase.
Escalation phase: the study utilised the Bayesian Logistic Regression Model (BLRM), incorporating escalation with overdose control (EWOC), which is a well established method for dose escalation in oncology trials. Following this process, successive cohorts of 3 newly enrolled patients received increasing doses of ruxolitinib and panobinostat until the maximum tolerated dose (MTD) or recommended phase II dose (RPIID) was determined. Once the MTD and/or RPIID were suspected in a minimum of 3 patients, additional patients were enrolled to the same cohort level to reach a minimum of 9 evaluable patients. The process also included safety, PK/PD assessments and estimates of efficacy based on measures of splenic reduction at each dose level.
Expansion: following the determination of the MTD and/or RPIID, a dose expansion phase was conducted at that dose to further define the safety and tolerability of the combination. At least 13, and no more than 23, additional patients were to be enrolled into the expansion phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: panobinostat, Drug: ruxolitinibSubjects will be treated with ruxolitinib 5 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 2 | Experimental | Drug: panobinostat, Drug: ruxolitinibSubjects will be treated with ruxolitinib 10 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 3 | Experimental | Drug: panobinostat, Drug: ruxolitinibSubjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 10 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 4 | Experimental | Drug: panobinostat, Drug: ruxolitinibSubjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 15 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 5 | Experimental | Drug: panobinostat, Drug: ruxolitinibSubjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 20 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
| Cohort 6/6+ | Experimental | Drug: panobinostat, Drug: ruxolitinibSubjects will be treated with ruxolitinib 15 mg twice daily (BID) and panobinostat 25 mg three times per week (TIW) every other week (QOW) on a 28 day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of myelofibrosis, either PMF, PPV or PET MF
- Palpable splenomegaly ≥ 5cm
- May have been previously treated with either panobinostat or ruxolitinib (unless discontinued for clinically relevant toxicities)
- Acceptable lab ranges for all organ systems
- Specifically: Platelet count > 100,000 not reached with the aide of transfusions
Key exclusion criteria (9 listed)
- Active malignancy
- Clinically significant heart disease
- Splenic irradiation within 12 months of starting study drug
- Need for ongoing systemic anticoagulation with the exception of Aspirin < 150mg/day or Low Molecular Weight Heparin
- History of platelet dysfunction or bleeding disorder in the 6 months prior to screening
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 |
|---|---|---|
| panobinostatAlso: LBH589Given 3 times a week, every other week in 28-day cycles. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6/6+ |
| ruxolitinibAlso: INC424Given twice daily in 28-day cycles. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6/6+ |
Primary outcome
Rate of dose limiting toxicities at the different dose levels
Time frame: Cycle 1 (a cycle = 28 days)
4 secondary outcomes
Rate of adverse events, serious adverse events, notable laboratory, vital signs and ECG results by dose level
Time frame: From screening until safety follow up visit (30 days after last treatment), approx. 8.5 years
AUC of ruxolitinib and panobinostat at various dose levels
Time frame: Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7
Cmax of ruxolitinib and panobinostat at various dose levels
Time frame: Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7
Tmax of ruxolitinib and panobinostat at various dose levels
Time frame: Ruxolitinib on days 1,2 and 6; Panobinostat on days 2-3 and days 6-7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2021.
- Novartis Clinical Trials results databaseLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing panobinostat and ruxolitinib in people with Idiopathic Myelofibrosis and Post Essential Thrombocythemia Myelofibrosis, run by Novartis Pharmaceuticals at 10 sites in 5 countries.
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 8 inclusion and 9 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 25 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy, France, Germany, Ireland, United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Rate of dose limiting toxicities at the different dose levels (time frame: Cycle 1 (a cycle = 28 days)). 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 25 Jun 2021.