Clinical Trial: Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior Therapy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Single-arm Dose-finding Phase Ib Multicenter Study of the Oral Smoothened Antagonist LDE225 in Combination With Nilotinib in Chronic or Accelerated Phase of Chronic Myeloid Leukemia Patients Who Hav

Brief Summary: The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy [ Time Frame: 56 days (2 treatment cycles at 28 days each) ]

Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225


Original Primary Outcome: Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy [ Time Frame: 56 days (2 treatment cycles at 28 days each) ]

Current Secondary Outcome:

  • No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms [ Time Frame: 336 days (12 treatment cycles) ]
    Assessment of the safety and tolerability profile of nilotinib in combination with LDE225
  • Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC) [ Time Frame: 50 days ]
    Assessment of the PK characteristics of nilotinib administered in combination with LDE225
  • Major molecular response (MMR) rates at 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ]
    Determination of the kinetics of major molecular response
  • Complete molecular response (CMR) rates at 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ]
    Determination of the kinetics of complete molecular response
  • Major cytogenic response (MCyR) rates by 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ]
    Determination of major cytogenetic response rates
  • Complete cytogenic response (CCyR) rates by 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ]
    Determination of complete cytogenetic response rates


Original Secondary Outcome:

  • No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms [ Time Frame: 336 days (12 treatment cycles) ]
  • Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC) [ Time Frame: 50 days ]
  • Major molecular response (MMR) rates at 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ]
  • Complete molecular response (CMR) rates at 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ]
  • Major cytogenic response (MCyR) rates by 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ]
  • Complete cytogenic response (CCyR) rates by 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ]


Information By: Novartis

Dates:
Date Received: October 14, 2011
Date Started: January 2012
Date Completion:
Last Updated: September 1, 2016
Last Verified: September 2016