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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.
 
ClinicalTrials.gov Identifier: NCT01433445
Recruitment Status : Active, not recruiting
First Posted : September 14, 2011
Last Update Posted : May 26, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 27, 2011
First Posted Date  ICMJE September 14, 2011
Last Update Posted Date May 26, 2020
Actual Study Start Date  ICMJE November 1, 2011
Estimated Primary Completion Date June 22, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2013)
Rate of dose limiting toxicities at the different dose levels [ Time Frame: Baseline, end of Cycle 1 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2011)
Percentage of Responders as measured by a change in spleen length of at least 50% reduction as determined by manual palpation; from Baseline (Cycle 1 Day 1) to Week 12, and maintained until Week 24 [ Time Frame: Baseline, Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2013)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • AUC and Cmax of ruxolitinib and panobinostat at various dose levels [ Time Frame: Cycle 1 Day 1, up to Cycle 1 Day 6 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2011)
  • 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 ]
  • 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 48 ]
  • 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, Week 5, Week 25, Week 49 ]
  • 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, End of Treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Panobinostat and Ruxolitinib in Primary Myelofibrosis, Post-polycythemia Vera-myelofibrosis or Post-essential Thrombocythemia-myelofibrosis
Official Title  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Idiopathic Myelofibrosis
  • Post Essential Thrombocythemia Myelofibrosis
  • Post Polycythemia-Vera Myelofibrosis
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Interventions:
  • Drug: panobinostat
  • Drug: ruxolitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 26, 2013)
61
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2011)
45
Estimated Study Completion Date  ICMJE June 22, 2020
Estimated Primary Completion Date June 22, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Ireland,   Italy,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01433445
Other Study ID Numbers  ICMJE CLBH589X2106
2011-000861-10 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP