Clinical Trial: Panobinostat and Ruxolitinib In MyElofibrosis (PRIME Trial)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Panobinostat and Ruxolitinib In MyElofibrosis (PRIME STUDY) - Phase I/II Study of Combination Oral JAK2 Tyrosine Kinase Inhibitor (JAK2-TKI) and Histone Deacetylase Inhibi

Brief Summary: This is a single-center, single arm, dose finding study to assess safety and tolerability of the oral combination of Panobinostat and Ruxolitinib in patients with myelofibrosis (MF) in chronic and accelerated phase.

Detailed Summary: Phase I/II open label, single institution, combination therapy trial of induction Ruxolitinib followed by combination with Panobinostat in dose escalation cohorts with a primary endpoint of determining the safety and tolerability of combination therapy in patients with myelofibrosis (MF) in chronic and accelerated phase. A 3+3standard dose escalation scheme will be employed and the occurrence of dose limiting toxicities (DLTs) will be captured and the occurrence of such events will determine dose cohort escalation by predetermined and established rules. In addition to establishing the DLTs, maximally tolerated dose (MTD), and recommended phase II dose (RPTD) in the phase I portion of this trial, exploratory biomarkers will be evaluated within phase I as well. Pharmacodynamics and exploratory genetic and epigenetic biomarkers will be explored as predictors of response to therapy. The RPTD cohort will be expanded to incorporate a total of 22 patients, including 6 from phase I, in order to assess clinical response as assessed by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) as a primary endpoint for the phase II portion of this trial.
Sponsor: John Mascarenhas

Current Primary Outcome:

• number of patients that experience adverse events [ Time Frame: at least 28 days ]
  Assess the safety and tolerability of Ruxolitinib in combination with Panobinostat in patients with MF
• proportion of patients that achieve at least stable disease [ Time Frame: at least 6 months ]
  Assess treatment response as defined by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Spleen size [ Time Frame: up to 14 months ]
  Assess changes in spleen size by palpation and MRI
• exploratory biomarkers [ Time Frame: up to 14 months ]
  o evaluate changes in inflammatory cytokines to therapy
• symptom response [ Time Frame: at least 6 months ]
  Assess symptom response with a validated MPN tool (MPN-SAF)

Original Secondary Outcome: Same as current

Information By: Icahn School of Medicine at Mount Sinai

Dates:
Date Received: September 14, 2012
Date Started: January 2013
Date Completion: December 2017
Last Updated: January 16, 2017
Last Verified: January 2017