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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Novartis
Sponsor:
Collaborators:
Children's Oncology Group
Innovative Therapies For Children with Cancer Consortium
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01844765
First received: April 29, 2013
Last updated: April 19, 2016
Last verified: April 2016
  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).

Condition Intervention Phase
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
Drug: nilotinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Rate of Major Molecular Responder (MMR) by BCR-ABL RQ-PCR analysis from peripheral blood by 12 cycles [ Time Frame: 12 cycles ] [ Designated as safety issue: No ]
    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.

  • Rate of CCyR at 12 cycles [ Time Frame: 12 cycles ] [ Designated as safety issue: No ]
    Newly diagnosed Ph+ CML-CP patients will be counted as Complete Cytogenetic Responder (CCyR) at 12 cycles if CCyR criteria is achieved at cycle 12 visit.

  • Rate of Major Molecular Responder (MMR) by BCR-ABL RQ-PCR analysis from peripheral blood at 6 cycles [ Time Frame: 6 cycles ] [ Designated as safety issue: No ]
    Resistant/intolerant Ph+ CML CP patients will be counted as Major Molecular Responder (MMR) at 6 cycles if the MMR criteria is achieved at cycle 6 visit.

  • Rate of Confirmed Hematological Responder (CHR) measured by complete blood count by 3 cycles [ Time Frame: 3 cycles ] [ Designated as safety issue: No ]
    Resistant/intolerant Ph+ CML advanced phase (AP) patients will be counted as Complete Hematological Responder (CHR) by 3 cycles if the CHR criteria is achieved at least once anytime between first study drug intake and cycle 3 visit.


Secondary Outcome Measures:
  • Time to response [ Time Frame: up to 66 cycles ] [ Designated as safety issue: No ]
    Time to response is defined as the time from the date of first study drug intake to the date of the first specified response.

  • Duration of response [ Time Frame: up to 66 cycles ] [ Designated as safety issue: No ]
    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.

  • Time to Disease Progression [ Time Frame: up to 66 cycles ] [ Designated as safety issue: No ]
    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.

  • Overall survival (OS) [ Time Frame: up to 66 cycles ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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

  • Pharmacodynamics [ Time Frame: up to 66 cycles ] [ Designated as safety issue: No ]
    BCR-ABL transcript levels determined with standard protocols in peripheral blood and bone marrow for all time points with available data

  • Rate of MMR [ Time Frame: 3, 6, 9,12, 18,24, 36, 48, 66 ] [ Designated as safety issue: No ]
    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

  • Event Free Survival [ Time Frame: up to 66 cycles ] [ Designated as safety issue: No ]
    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)

  • Rate of Cytogenetic Response category [ Time Frame: 6, 12, 18, 24, 36, 48, 66 cycles ] [ Designated as safety issue: No ]
    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

  • Rate of CHR [ Time Frame: 3,6, 9, 12, 18, 24, 36, 48, 66 ] [ Designated as safety issue: No ]
    Rate of CHR in newly diagnosed Ph+ CML-CP and AP patients resistant/intolerant to either imatinib or dasatinib by designated timepoints

  • PK profile of nilotinib in pediatric patients [ Time Frame: up to 12 cycles ] [ Designated as safety issue: Yes ]
    Population PK parameters of nilotinib

  • Emerging signs of resistance [ Time Frame: up to 66 cycles ] [ Designated as safety issue: No ]
    Mutational assessment of BCR-ABL

  • Long term effect of nilotinib on growth, development and maturation [ Time Frame: up to 66 cycles ] [ Designated as safety issue: Yes ]
    Assessment of development (growth and sexual maturation) and thyroid function

  • Further characterize safety and tolerability [ Time Frame: up to 66 cycles ] [ Designated as safety issue: Yes ]
    Incidence and severity of adverse events, as assessed by patient symptoms, physical exam assessments, abnormal laboratory tests, echocardiograms and electrocardiograms

  • Acceptability of study drug formulation [ Time Frame: day1, day 28, early discontinuation or month 12 ] [ Designated as safety issue: No ]
    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).


Other Outcome Measures:
  • Long term effect on nilotinib on bone metabolism [ Time Frame: up to 66 cycles ] [ Designated as safety issue: Yes ]
    Alteration of bone biochemical markers, DEXA and X-Ray


Estimated Enrollment: 70
Study Start Date: August 2013
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Newly diagnosed and untreated Ph+ CML in first chronic phase
Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Drug: nilotinib
Nilotinib will be administered at 230mg/m2 ,twice daily for up to 66 cycles (1 cycle = 28 days). Drug will be supplied in 50mg, 150mg,and 200mg capsules. Dose administration will be rounded to the nearest 50mg dose (to a maximum dose of 400mg).
Other Name: Tasigna, AMN107
Experimental: Resistant/intolerant Ph+ CML in chronic phase
Resistant or Intolerant to either imatnib or dasatnib
Drug: nilotinib
Nilotinib will be administered at 230mg/m2 ,twice daily for up to 66 cycles (1 cycle = 28 days). Drug will be supplied in 50mg, 150mg,and 200mg capsules. Dose administration will be rounded to the nearest 50mg dose (to a maximum dose of 400mg).
Other Name: Tasigna, AMN107
Experimental: Resistant/intolerant Ph+ CML in accelerated phase
Resistant or intolerant to either imatnib or dasatnib
Drug: nilotinib
Nilotinib will be administered at 230mg/m2 ,twice daily for up to 66 cycles (1 cycle = 28 days). Drug will be supplied in 50mg, 150mg,and 200mg capsules. Dose administration will be rounded to the nearest 50mg dose (to a maximum dose of 400mg).
Other Name: Tasigna, AMN107

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01844765

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 88 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Children's Oncology Group
Innovative Therapies For Children with Cancer Consortium
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01844765     History of Changes
Other Study ID Numbers: CAMN107A2203 
Study First Received: April 29, 2013
Last Updated: April 19, 2016
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Hungary: National Institute for Quality- and Organizational Development in Healthcare and Medicines, National Institute of Pharmacy
Italy: National Institute of Health
South Korea: Korea Food and Drug Administration (KFDA)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Netherlands: Ministry of Health, Welfare and Sport
Thailand: Food and Drug Administration
Australia: National Health and Medical Research Council
New Zealand: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Turkey: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
France: ANSM

Keywords provided by Novartis:
Tasigna
nilotinib treatment
chronic phase
Ph+ CML
accelerated phase
newly diagnosed Ph+ CML
pediatric
24 month treatment

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Neoplastic Processes
Neoplasms by Histologic Type
Neoplasms
Pathologic Processes

ClinicalTrials.gov processed this record on July 27, 2016