This trial is active, not recruiting.

Conditions idiopathic myelofibrosis, post essential thrombocythemia myelofibrosis, post polycythemia-vera myelofibrosis
Treatments panobinostat, ruxolitinib
Phase phase 1
Targets HDAC, JAK, HIF-1a, JAK1, JAK2, VEGF
Sponsor Novartis Pharmaceuticals
Start date November 2011
End date December 2016
Trial size 61 participants
Trial identifier NCT01433445, 2011-000861-10, CLBH589X2106


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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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
panobinostat LBH589
Given 3 times a week, every other week in 28-day cycles.
ruxolitinib INC424
Given twice daily in 28-day cycles.

Primary Outcomes

Rate of dose limiting toxicities at the different dose levels
time frame: Baseline, end of Cycle 1

Secondary Outcomes

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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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)
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Novartis.