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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01433445
First received: June 27, 2011
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Idiopathic Myelofibrosis
Post Essential Thrombocythemia Myelofibrosis
Post Polycythemia-Vera Myelofibrosis
Drug: panobinostat
Drug: ruxolitinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Rate of dose limiting toxicities at the different dose levels [ Time Frame: Baseline, end of Cycle 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • AUC and Cmax of ruxolitinib and panobinostat at various dose levels [ Time Frame: Cycle 1 Day 1, up to Cycle 1 Day 6 ] [ Designated as safety issue: No ]

Estimated Enrollment: 61
Study Start Date: November 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 after stopping study treatment
  • Other protocol-defined inclusion/exclusion criteria may apply
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01433445

Contacts
Contact: Novartis Pharmaceuticals +41613241111 clinicaltrial.enquiries@novartis.com
Contact: Novartis Pharmaceuticals

Locations
France
Novartis Investigative Site Recruiting
Paris, France, 75010
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site Active, not recruiting
Magdeburg, Germany, 39120
Novartis Investigative Site Active, not recruiting
Mainz, Germany, 55131
Ireland
Novartis Investigative Site Active, not recruiting
Dublin, Ireland, Dublin 8
Novartis Investigative Site Active, not recruiting
Galway, Ireland
Italy
Novartis Investigative Site Active, not recruiting
Firenze, FI, Italy, 50134
Novartis Investigative Site Active, not recruiting
Reggio Calabria, RC, Italy, 89124
Novartis Investigative Site Active, not recruiting
Varese, VA, Italy, 21100
United Kingdom
Novartis Investigative Site Active, not recruiting
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01433445     History of Changes
Other Study ID Numbers: CLBH589X2106, 2011-000861-10
Study First Received: June 27, 2011
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: IMB (Irish Medicines Board)
Italy: AIFA (Agenzia Italiana del Farmaco)
Germany: BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte)
France: AFSSAPS (Agence française de sécurité sanitaire des produits de santé)

Keywords provided by Novartis:
Myelofibrosis
Panobinostat
Ruxolitinib
MF
PMF
PPV
PPV-MF
PET
PET-MF
JAK2
DACi

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocythemia, Essential
Thrombocytosis
Blood Coagulation Disorders
Blood Platelet Disorders
Bone Marrow Diseases
Hematologic Diseases
Hemorrhagic Disorders
Myeloproliferative Disorders
Panobinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014