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

December 6, 2020 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
  • France
      • Marseille, France, 13273
        • Novartis Investigative Site
  • Germany
      • Frankfurt, Germany, 60590
        • Novartis Investigative Site
      • Ulm, Germany, 89081
        • Novartis Investigative Site
  • Italy
    • RM
      • Roma, RM, Italy, 00161
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28006
        • Novartis Investigative Site
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: Nilotinib + LDE225
Nilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
56 days (2 treatment cycles at 28 days each)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
336 days (12 treatment cycles)
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
50 days
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
336 days (12 treatment cycles)
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
336 days (12 treatment cycles)
Major cytogenic response (MCyR) rates by 3, 6 and 12 months
Time Frame: 336 days (12 treatment cycles)
Determination of major cytogenetic response rates
336 days (12 treatment cycles)
Complete cytogenic response (CCyR) rates by 3, 6 and 12 months
Time Frame: 336 days (12 treatment cycles)
Determination of complete cytogenetic response rates
336 days (12 treatment cycles)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 14, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 20, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 21, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 9, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAMN107Y2101
  • 2011-000282-12 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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