Clinical Trials /

Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

NCT01844765

Description:

To evaluate the safety, efficacy and concentration of nilotinib over time in the Ph+ chronic myelogenous leukemia (CML) in pediatric patients (from 1 to <18 years).

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.
  • Official Title: A Multi-center, Open Label, Non-controlled Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Pediatric Patients With Newly Diagnosed Ph+ Chronic Myelogenous Leukemia (CML) in Chronic Phase (CP) or With Ph+ CML in CP or Accelerated Phase (AP) Resistant or Intolerant to Either Imatinib or Dasatinib

Clinical Trial IDs

  • ORG STUDY ID: CAMN107A2203
  • NCT ID: NCT01844765

Conditions

  • Leukemia
  • Leukemia,Pediatric
  • Leukemia, Myleiod
  • Leukemia, Mylegenous, Chronic
  • Leukemia, Mylegenous, Accelerated
  • BCR-ABL Positive
  • Myeloproliferative Disorder
  • Bone Marrow Disease
  • Hematologic Diseases
  • Neoplastic Processes
  • Imatinib
  • Dasatinib
  • Enzyme Inhibitor
  • Protein Kinase Inhibitor

Interventions

DrugSynonymsArms
nilotinibTasigna, AMN107Newly diagnosed and untreated Ph+ CML in first chronic phase

Purpose

To evaluate the safety, efficacy and concentration of nilotinib over time in the Ph+ chronic myelogenous leukemia (CML) in pediatric patients (from 1 to <18 years).

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Newly diagnosed and untreated Ph+ CML in first chronic phaseExperimentalDiagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
  • nilotinib
Resistant/intolerant Ph+ CML in chronic phaseExperimentalResistant or Intolerant to either imatnib or dasatnib
  • nilotinib
Resistant/intolerant Ph+ CML in accelerated phaseExperimentalResistant or intolerant to either imatnib or dasatnib
  • nilotinib

Eligibility Criteria

Inclusion Criteria:

- Newly diagnosed and untreated Ph+ CML CP or Ph+ CML CP or AP resistant or intolerant to either imatinib or dasatinib

- Karnofsky or Lansky ≥ 50

- Adequate renal, hepatic and pancreatic function

- Potassium, magnesium, phosphorus and total calcium values ≥ LLN (lower limit of normal)

- Written informed consent

Exclusion Criteria:

- Treatment with strong CYP3A4 inhibitors or inducers

- Use or planned use of any medications that have a known risk or possible risk to prolong the QT interval

- Acute or chronic liver, pancreatic or severe renal disease

- History of pancreatitis or chronic pancreatitis.

- Impaired cardiac function

- No evidence of active graft vs host and <3mo since Stem Cell Transplant

- Total body irradiation (TBI) or craniospinal radiation therapy <6months

- Hypersensitivity to the active ingredient or any of the excipients including lactose.

- Other protocol-defined inclusion/exclusion criteria.

Maximum Eligible Age:17 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Major Molecular Responder (MMR) by BCR-ABL RQ-PCR analysis from peripheral blood by 12 cycles
Time Frame:12 cycles
Safety Issue:
Description:Newly diagnosed Ph+ CML chronic phase (CP) patients will be counted as Major Molecular Responder (MMR) by 12 cycles if the MMR criteria is achieved at least once any time between first study drug intake and cycle 12 visit.

Secondary Outcome Measures

Measure:Time to response
Time Frame:up to 66 cycles
Safety Issue:
Description:Time to response is defined as the time from the date of first study drug intake to the date of the first specified response.
Measure:Duration of response
Time Frame:up to 66 cycles
Safety Issue:
Description:Duration of a response is defined as the time between the date of the first specified response to either the date for confirmed loss of the response or progression to advance phase (AP)/BC (from CP) or to BC (from AP) or CML-related death, whichever is earlier.
Measure:Time to Disease Progression
Time Frame:up to 66 cycles
Safety Issue:
Description:Time to disease progression is defined as the time from the date of first study drug intake to the date of the event defined as the first progression to AP/BC (from CP) or to BC (from AP) or the date of CML-related death, whichever is earlier.
Measure:Overall survival (OS)
Time Frame:up to 66 cycles
Safety Issue:
Description:Overall survival is defined as the time from the date of first study drug intake to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of their last assessment for patients on study and date of last contact for patients in follow-up.
Measure:Rate of major cytogenetic response (MCyR) and confirmed cytogenetic response (CCyR) in Newly diagnosed Ph+ CML and in Ph+ CML-AP patients resistant/intolerant to either imatinib or dasatinib
Time Frame:6, 12, 18, 24, 36, 48, 66 cycles
Safety Issue:
Description:Rate of major cytogenetic response (MCyR) and confirmed cytogenetic response (CCyR) in Newly diagnosed Ph+ CML and in Ph+ CML-AP patients resistant/intolerant to either imatinib or dasatinib by designated timepoints
Measure:Pharmacodynamics
Time Frame:up to 66 cycles
Safety Issue:
Description:BCR-ABL transcript levels determined with standard protocols in peripheral blood and bone marrow for all time points with available data
Measure:Rate of MMR
Time Frame:3, 6, 9,12, 18,24, 36, 48, 66
Safety Issue:
Description:Rate of MMR in newly diagnosed Ph+ CML CP and in Ph+ CML CP and AP patients resistant/intolerant to either imatinib or dasatnib by designated timepoints
Measure:Event Free Survival
Time Frame:up to 66 cycles
Safety Issue:
Description:Event Free Survival is defined as the time from the date of first study drug intake to the first occurrence of any of the following loss of CHR, loss of MCyR ( PCyR + CCyR), progression to AP/BC (from CP) or to BC (from AP), or death from any cause. (Including events only during treatment)
Measure:Rate of Cytogenetic Response category
Time Frame:6, 12, 18, 24, 36, 48, 66 cycles
Safety Issue:
Description:Rate of cytogenetic response (complete, partial, major, minor, minimal and no response) in Ph+ CML-CP resistant/intolerant to imatinib or dasatinib by 6, 12, 18,24, 36, 48 and 66 cycles
Measure:Rate of CHR
Time Frame:3,6, 9, 12, 18, 24, 36, 48, 66
Safety Issue:
Description:Rate of CHR in newly diagnosed Ph+ CML-CP and AP patients resistant/intolerant to either imatinib or dasatinib by designated timepoints
Measure:PK profile of nilotinib in pediatric patients
Time Frame:up to 12 cycles
Safety Issue:
Description:Population PK parameters of nilotinib
Measure:Emerging signs of resistance
Time Frame:up to 66 cycles
Safety Issue:
Description:Mutational assessment of BCR-ABL
Measure:Long term effect of nilotinib on growth, development and maturation
Time Frame:up to 66 cycles
Safety Issue:
Description:Assessment of development (growth and sexual maturation) and thyroid function
Measure:Further characterize safety and tolerability
Time Frame:up to 66 cycles
Safety Issue:
Description:Incidence and severity of adverse events, as assessed by patient symptoms, physical exam assessments, abnormal laboratory tests, echocardiograms and electrocardiograms
Measure:Acceptability of study drug formulation
Time Frame:day1, day 28, early discontinuation or month 12
Safety Issue:
Description:Questionnaire to capture patient assessment of palatability (very good to very bad) and acceptability of taking the medication (very easy to very hard to administration).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Tasigna
  • nilotinib treatment
  • chronic phase
  • Ph+ CML
  • accelerated phase
  • newly diagnosed Ph+ CML
  • pediatric
  • 24 month treatment

Last Updated

March 20, 2017