E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- leukemia
- leukemia,pediatric
- leukemia, myleiod
- leukemia, mylegenous, chronic
- leukemia, mylegenous, accelerated
- BCR-ABL positive
- myeloproliferative disorder
- bone marrow disease
- hematologic diseases
- neoplastic processes |
CML bij kinderen |
|
E.1.1.1 | Medical condition in easily understood language |
pediatric blooddisease |
bloedziekte bij kinderen |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054352 |
E.1.2 | Term | Chronic phase chronic myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To assess efficacy of nilotinib in pediatric patients with Ph+ CML CP resistant or intolerant to either imatinib or dasatinib
2. To assess efficacy of nilotinib in pediatric patients with Ph+ CML AP resistant or intolerant to either imatinib or dasatinib
3. To assess efficacy of nilotinib in pediatric patients with newly diagnosed Ph+ CML CP |
|
E.2.2 | Secondary objectives of the trial |
1. To further characterize efficacy and PK profile of nilotinib in pediatric patients with Ph+ CML
2. To further characterize safety and tolerability of nilotinib in pediatric patients with Ph+ CML
3. To assess long term effect on growth, development and maturation of nilotinib treatment in pediatric patients with Ph+ CML
4. To identify emerging signs of resistance to nilotinib
5. To describe acceptability of the study drug formulation |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to meet all of the following criteria; additional inclusion criteria may apply as per protocol:
1. Newly diagnosed and untreated Ph+ CML CP or Ph+ CML CP or AP resistant or intolerant to either imatinib or dasatinib
2. Karnofsky or Lansky ≥ 50
3. Adequate renal, hepatic and pancreatic function
4. Potassium, magnesium, phosphorus and total calcium values ≥ LLN (lower limit of normal)
5. Written informed consent
Additional inclusion criteria are defined in the protocol. |
|
E.4 | Principal exclusion criteria |
Patients eligible for this study must not meet any of the following criteria:
1. Treatment with strong CYP3A4 inhibitors or inducers
2. Use or planned use of any medications that have a known risk or possible risk to prolong the QT interval
3. Acute or chronic liver, pancreatic or severe renal disease
4. History of pancreatitis or chronic pancreatitis.
5. Impaired cardiac function
6. No evidence of active graft vs host and <3mo since Stem Cell Transplant
7. Total body irradiation (TBI) or craniospinal radiation therapy <6months 8. Hypersensitivity to the active ingredient or any of the excipients including lactose
Additional exclusion criteria are defined in the protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Rate of Major Molecular Response (MMR)
2. Rate of Complete Hematological Response (CHR)
3. Rate of Major Molecular Response (MMR)
4. Rate of Complete Cytogenetic Response (CCyR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At 6 cycles
2. By 3 cycles
3. By 12 cycles
4. At 12 cycles |
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E.5.2 | Secondary end point(s) |
1. Rate of MCyR and CCyR
2. Rate of each cytogenetic response category
3. Rate of MMR and CHR
4. Time to response, duration of response, time to disease progression, overall survival, event free survival
5. Population pharmacokinetic parameters of nilotinib
6. Pharmacodynamics (BCR-ABL transcript levels determined with standard protocols in peripheral blood)
7. Safety and tolerability: incidence and severity of adverse events, as assessed by patient symptoms, physical exam assessments, abnormal laboratory tests, echocardiograms and electrocardiograms
8. Assessment of development (growth and sexual maturation), and thyroid function
9. Mutational assessment of BCR-ABL
10.Questionnaire on acceptability (including palatability) of dose forms used after first dose, cycle 1 and cycle 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. By 6, 12, 18, 24, 36, 48, and 66 cycles
2. By 6, 12, 18, 24, 36, 48, and 66 cycles
3. By 3, 6, 9, 12, 18, 24, 36, 48, and 66 cycles
4. Up to 66 cycles
5. Up to 66 cycles
6. Continuous
7. Up to 66 cycles
8. Up to 66 cycles
9. Up to 66 cycles
10. After 1st dose, cycle 1, and cycle 12 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
acceptability of study drug formulation (including palatability) |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Netherlands |
New Zealand |
Russian Federation |
Spain |
Thailand |
Turkey |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of study is defined as the timepoint when all patients have completed the study evaluation completion (SEC) visit. The SEC will either be a minimum of 30 days post Cycle 66 or a minimum of 30 days post early discontinuation. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |