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

This study is currently recruiting participants.
Verified April 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01456676
First received: October 14, 2011
Last updated: April 5, 2013
Last verified: April 2013
History of Changes

October 14, 2011
April 5, 2013
January 2012
October 2013   (final data collection date for primary outcome measure)
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) ] [ Designated as safety issue: Yes ]
Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225
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) ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01456676 on ClinicalTrials.gov Archive Site
  • 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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Determination of major cytogenetic response rates
  • Complete cytogenic response (CCyR) rates by 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ] [ Designated as safety issue: No ]
    Determination of complete cytogenetic response rates
  • 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) ] [ Designated as safety issue: Yes ]
  • Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC) [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Major molecular response (MMR) rates at 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ] [ Designated as safety issue: No ]
  • Complete molecular response (CMR) rates at 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ] [ Designated as safety issue: No ]
  • Major cytogenic response (MCyR) rates by 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ] [ Designated as safety issue: No ]
  • Complete cytogenic response (CCyR) rates by 3, 6 and 12 months [ Time Frame: 336 days (12 treatment cycles) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior Therapy
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 Have Failed Prior Therapy With Other BCR-ABL Tyrosine-kinase Inhibitors

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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
Drug: Nilotinib + LDE225
Nilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL.
Experimental: Nilotinib + LDE225
The planned dose of nilotinib 400 mg b.i.d (twice a day) was selected for the combination as this is the dose approved for the treatment of the patient population that will be included in the present study. The starting dose for LDE225 chosen for the current study is 400 mg once daily(q.d.). The maximum dose of LDE225 that will be tested in combination with nilotinib is 800 mg once dail.y
Intervention: Drug: Nilotinib + LDE225
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
September 2016
October 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Philadelphia chromosome positive (Ph+) CML in chronic phase (CP) or accelerated phase (AP)with resistance to at least one prior BCR-ABL targeting TKI
  2. Documented chronic phase CML
  3. Adequate end organ function
  4. Female patients of childbearing potential must have a negative serum pregnancy test and must be using highly effective methods of contraception. Male patients with female partners of child-bearing potential must use condoms.

Exclusion Criteria:

  1. Impaired cardiac function
  2. Severe and/or uncontrolled concurrent disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
  3. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
  4. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to entering the study
  5. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug.
  6. Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation

Other protocol-defined inclusion/exclusion criteria may apply.
Both
18 Years and older
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Belgium,   Canada,   France,   Germany,   Italy,   Korea, Republic of,   Singapore,   Spain
 
NCT01456676
CAMN107Y2101, 2011-000282-12
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2013

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