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Panobinostat and Ruxolitinib in Primary Myelofibrosis, Post-polycythemia Vera-myelofibrosis or Post-essential Thrombocythemia-myelofibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01433445
Recruitment Status : Completed
First Posted : September 14, 2011
Last Update Posted : July 7, 2020
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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 Myelofibrosis (PPV MF).

Condition or disease Intervention/treatment Phase
Idiopathic Myelofibrosis Post Essential Thrombocythemia Myelofibrosis Post Polycythemia-Vera Myelofibrosis Drug: panobinostat Drug: ruxolitinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 1, 2011
Actual Primary Completion Date : June 22, 2020
Actual Study Completion Date : June 22, 2020

Arm Intervention/treatment
Experimental: panobinostat + ruxolitinib
Escalating doses of ruxolitinib from 5 mg BID to 15 mg BID in combination with panobinostat from 10 to 30 mg tiw QOW depending on determination of MTD of each drug
Drug: panobinostat
Given 3 times a week, every other week in 28-day cycles.
Other Name: LBH589

Drug: ruxolitinib
Given twice daily in 28-day cycles.
Other Name: INC424

Primary Outcome Measures :
  1. Rate of dose limiting toxicities at the different dose levels [ Time Frame: Baseline, end of Cycle 1 ]

Secondary Outcome Measures :
  1. Percentage of Responders achieving at least a 35% reduction in splenic volume (compared to baseline) at Week 12, or end of study, whichever comes first as determined by MRI/CT [ Time Frame: Baseline, Week 12 ]
  2. Percentage of responders as measured by improvement in bone marrow fibrosis as graded according to the International Working Group consensus criteria for treatment response as compared to baseline [ Time Frame: Baseline, Week 24 and 48 ]
  3. Percentage of Responders as measured by Summary statistics in absolute values at each visit and absolute and percentage change from baseline at each visit for change in JAK2V617F allele burden and cytokine measurement [ Time Frame: Baseline, up to Week 48 ]
  4. Proportion of patients who are transfusion dependent, as well as, the proportion of patients whose transfusion status (dependent or independent) changed (from dependent to independent or vice versa) at each cycle as compared to baseline [ Time Frame: Baseline, up to End of Treatment ]
  5. Percentage of Responders as measured by a change in spleen length of at least 50% reduction as determined by manual palpation from Baseline to Week 12 and maintained until Week 24 [ Time Frame: Baseline, Week 12 and 24 ]
  6. Rate of adverse events, serious adverse events, notable laboratory, vital signs and ECG results by dose level [ Time Frame: baseline, up to end of study ]
  7. AUC and Cmax of ruxolitinib and panobinostat at various dose levels [ Time Frame: Cycle 1 Day 1, up to Cycle 1 Day 6 ]

Information from the National Library of Medicine

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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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
  • Other protocol-defined inclusion/exclusion criteria may apply

Information from the National Library of Medicine

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 identifier (NCT number): NCT01433445

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Novartis Investigative Site
Paris, France, 75010
Novartis Investigative Site
Villejuif Cedex, France, 94805
Novartis Investigative Site
Magdeburg, Germany, 39120
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Dublin, Ireland, DUBLIN 8
Novartis Investigative Site
Galway, Ireland
Novartis Investigative Site
Firenze, FI, Italy, 50134
Novartis Investigative Site
Reggio Calabria, RC, Italy, 89124
Novartis Investigative Site
Varese, VA, Italy, 21100
United Kingdom
Novartis Investigative Site
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT01433445    
Other Study ID Numbers: CLBH589X2106
2011-000861-10 ( EudraCT Number )
First Posted: September 14, 2011    Key Record Dates
Last Update Posted: July 7, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Additional relevant MeSH terms:
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Polycythemia Vera
Primary Myelofibrosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action