Study of efficacy and safety of nilotinib in pediatric CML patients

• Register: EUCTR
• Last refreshed on: 2 August 2021
• Main ID: EUCTR2013-000200-41-ES
• Date of registration: 13/06/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica, S.A.
• Public title: Study of efficacy and safety of nilotinib in pediatric CML 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: 09/08/2013
• Target sample size: 70
• 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: yes; 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, Netherlands, New Zealand, Russian Federation, Spain, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Departamento Médico Oncología (GMO)
• Affiliation: Novartis Farmacéutica, S.A.

• Name: Departamento Médico Oncología (GMO)
• Affiliation: Novartis Farmacéutica, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study have to meet all of the following criteria:
1.Male or female patients from 1 year of age to less than 18 years of age at study entry.
2.Patients must have the diagnosis of newly diagnosed and untreated Ph+ CML CP or Ph+ CML CP or AP resistant or intolerant to either imatinib or dasatinib
3.Performance status: Karnofsky ? 50% for patients > 10 years of age, and Lansky ? 50 for patients ? 10 years of age.
4.Patients must have adequate renal, hepatic and pancreatic function
5.Patients must have potassium, magnesium, phosphorus and total calcium values ? LLN (lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of study medication.
Written informed consent must be obtained prior to any screening procedures.
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Female patients of childbearing potential who do not agree to abstinence or, if sexually active, do not agree to the use of contraception as defined in Section 7.2.2.5.5.
2.Patients actively receiving therapy with strong CYP3A4 inhibitors or inducers and the treatment cannot be either discontinued or switched to a different medication at least 14 days prior to starting study drug.
3.Patients who are currently receiving treatment with any medications that have a known risk or possible risk to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. A list of QT prolonging compounds can be found at http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm.
4.Acute or chronic liver, pancreatic or severe renal disease considered unrelated to CML.
5.History of pancreatitis within 12 months of starting study drug or past medical history of chronic pancreatitis.
6.Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, uncontrolled infection)
7.Impaired cardiac function
8.Patients with a known T315I mutation in BCR-ABL.
9.Previous treatment with more than one TKI for imatinib or dasatinib resistant/intolerant Ph+ CML patients. Previous treatment with any TKI for newly diagnosed Ph+ CML patients.
10.Patients who have received myelosuppressive chemotherapy less than 3 weeks prior to first dose of study drug.
11.Patients who have not recovered from all acute toxicities from all prior myelosuppressive chemotherapy prior to starting study drug.
12.Patients who have received hematopoietic growth factors within 7 days of starting study drug.
13.Patients who have received Pegfilgrastim (Neulasta®) within 14 days of starting study drug.
14.In case of Stem Cell Transplant (SCT) or Rescue without total body irradiation (TBI): Evidence of active graft vs. host disease and < 3 months since SCT.
15.In case of radiation therapy: less than 2 weeks if local palliative, less than 3 months after total body irradiation (TBI), or craniospinal radiation therapy or if at least 50% radiation of pelvis; less than 6 weeks after other substantial BM radiation.
16.Patients with known Hepatitis B, Hepatitis C, or HIV infection.
17.Patients who, in the opinion of the investigator, are unlikely to comply with the protocol or safety monitoring requirements.
18.Patients who are breast feeding
19.Patients who have a known hypersensitivity to the active ingredient or any of the excipients including lactose.


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

Health Condition(s) or Problem(s) studied

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

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
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: NILOTINIB
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: NILOTINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

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: NILOTINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: ?To characterize efficacy in pediatric patients with Ph+ CML.
?To further characterize PK in pediatric patients with Ph+ CML.
?To identify emerging signs of resistance to nilotinib.
?To describe acceptability of the study drug formulation.
?To further characterize safety and tolerability of nilotinib in pediatric patients with Ph+ CML.

Primary end point(s): Rate of MCyR by 12 months
Rate of complete hematological response (CHR) by 3 months
?Rate of MMR by 12 months by PCR analysis. MMR is defined as ? 0.1% BCR-ABL/control gene % by international scale, measured by RQ-PCR which is equivalent to ? 3 log reduction of BCR-ABL transcript from standardized
?Rate of MCyR by 12 months

Main Objective: ?To assess efficacy of nilotinib in pediatric patients with Ph+ CML CP resistant or intolerant to either imatinib or dasatinib.
?To assess efficacy of nilotinib in pediatric patients with Ph+ CML AP resistant or intolerant to either imatinib or dasatinib.
?To assess efficacy of nilotinib in pediatric patients with newly diagnosed Ph+ CML CP.

Timepoint(s) of evaluation of this end point: ?12 months
?12 months
? 3 months

Secondary Outcome(s)

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

Secondary end point(s): ?Time to response, duration of response, time to disease progression, overall survival
?Rate of MCyR and CCyR in newly diagnosed Ph+ CML CP and in Ph+ CML CP AP patients resistant/intolerant to either imatinib or dasatinib by 6, 12* and 24 months
?Rate of MMR by 3, 6, 9, 12* and 24 months in newly diagnosed Ph+ CML CP and Ph+ CML CP and AP patients resistant/intolerant to either imatinib or dasatinib
?Rate of CHR by 3*, 6, 9, 12 and 24 in newly diagnosed Ph+ CML CP and in Ph+ CML CP and AP patients resistant/intolerant to either imatinib or dasatinib
?Population PK parameters of nilotinib
?Pharmacodynamics (BCR-ABL transcript levels determined with standard protocols in peripheral blood and bone marrow)

Secondary ID(s)

CAMN107A2203

2013-000200-41-IT

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 05/07/2013
Contact:

Results

• Results available: Yes
• Date Posted: 13/03/2021
• Date Completed: 28/08/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000200-41/results