Open label, phase II study to evaluate efficacy and safety of oral nilotinib in Philadelphia positive (Ph+) chronic myelogenous leukemia (CML) pediatric patients.

• Register: EUCTR
• Last refreshed on: 23 November 2020
• Main ID: EUCTR2013-000200-41-NL
• Date of registration: 16/12/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Open label, phase II study to evaluate efficacy and safety of oral nilotinib in Philadelphia positive (Ph+) chronic myelogenous leukemia (CML) pediatric patients.
• Scientific 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
• Date of first enrolment: 20/12/2013
• Target sample size: 59
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000200-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, New Zealand, Russian Federation, Spain, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 59
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

- leukemia - leukemia,pediatric - leukemia, myleiod - leukemia, mylegenous, chronic - leukemia, mylegenous, accelerated - BCR-ABL positive - myeloproliferative disorder - bone marrow disease - hematologic diseases - neoplastic processes
MedDRA version: 21.0 Level: LLT Classification code 10054352 Term: Chronic phase chronic myeloid leukemia System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Tasigna
Product Name: nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Tasigna
Product Name: nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Product Name: nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: 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

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)

Secondary Objective: 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

Timepoint(s) of evaluation of this end point: 1. At 6 cycles
2. By 3 cycles
3. By 12 cycles
4. At 12 cycles

Secondary Outcome(s)

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

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

Secondary ID(s)

2013-000200-41-IT

CAMN107A2203

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 20/12/2013
Contact: