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: 10 March 2014
• Main ID: EUCTR2013-000200-41-IT
• Date of registration: 27/05/2013
• Prospective Registration: Yes
• Primary sponsor: NOVARTIS FARMA S.p.A.
• 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: 22/07/2013
• Target sample size: 70
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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: no 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

Countries of recruitment

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

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA S.p.A.

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA S.p.A.

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: 70
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

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

newly diagnosed Ph+ chronic myelogenous leukemia (CML) in chronic phase (CP) or Ph+ CML in CP or accelerated phase (AP) resistant or intolerant to either imatinib or dasatinib- bone marrow disease
MedDRA version: 14.1 Level: LLT Classification code 10054352 Term: Chronic phase chronic myeloid leukemia System Organ Class: 100000004864

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
Other descriptive name: ND
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
Other descriptive name: ND
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
Other descriptive name: ND
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

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 identify emerging signs of resistance to nilotinib
4. To describe acceptability of the study drug formulation

Timepoint(s) of evaluation of this end point: 1. 12 months
2. 12 months
3. 3 months

Primary end point(s): 1. Rate of Major Molecular Responder (MMR) by BCRABL RQ-PCR analysis from peripheral blood by 12 months
2. Rate of Major Cytogenetic Responder (MCyR) measured by the percentage of Ph+ metaphases in bone marrow by 12 months
3. Rate of Confirmed Hematological Responder (CHR) measured by complete blood count by 3 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. 1, 3, 6, 9, 12 months
2. up to 24 months
3. up to 24 months
4. up to 24 months or date of last contact in follow-up
5. up to 24 months
6. up to 24 months
7. up to 24 months

Secondary end point(s): 1. Time to response of primary endpoints
2. Duration of response
3. Time to disease progression
4. Overall Survival (OS)
5. Rate of major cytogenetic response (MCyR) and confirmed cytogenetic response (CCR) in all patients for timepoints not already analyzed in primary endpoints
6. BCR-ABL transcript levels determined with standard protocols in peripheral blood and bone marrow for all time points with available data
7. Rate of MMR and CHR in all patients for timepoints not already analyzed in primary endpoints

Secondary ID(s)

CAMN107A2203

Source(s) of Monetary Support

Novartis Pharma Services AG