Description:
To evaluate the safety, efficacy and pharmacokinetics of nilotinib over time in the Ph+ chronic myelogenous leukemia (CML) in pediatric patients (from 1 to <18 years).
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
Related Conditions:
- Chronic Myeloid Leukemia
Recruiting Status:
Completed
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
| Drug | Synonyms | Arms |
|---|---|---|
| nilotinib | Tasigna, AMN107 | Newly 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
| Name | Type | Description | Interventions |
|---|---|---|---|
| Newly diagnosed and untreated Ph+ CML in first chronic phase | Experimental | Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis. |
|
| Resistant/intolerant Ph+ CML in chronic phase | Experimental | Resistant or Intolerant to either imatnib or dasatnib |
|
| Resistant/intolerant Ph+ CML in accelerated phase | Experimental | Resistant or intolerant to either imatnib or dasatnib |
|
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
