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: 6 October 2020
• Main ID: EUCTR2013-000200-41-HU
• Date of registration: 21/06/2013
• 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: 12/09/2013
• 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

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

Contacts

• Name: Public Information Desk
• Affiliation: Novartis Hungary Kft.

• Name: Public Information Desk
• Affiliation: Novartis Hungary Kft.

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. Newly diagnosed Ph+ CML-CP or Ph+ CML-CP or AP resistant or intolerant to either imatinib or dasatinib (as defined in the protocol)
3. Performance status: Karnofsky =50% for patients >10 years of age, and Lansky =50 for patients =10 years of age.
4. Adequate renal, hepatic and pancreatic function as defined in the protocol
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
6. Written informed consent prior to any screening procedures. However, if requested tests were performed as part of clinical practice within the window required per protocol, this data can be used provided all parameters required per protocol were verified.
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. Female patients who are : (a) pregnant, (b) of childbearing potential without a negative hCG pregnancy test prior to baseline and (c) female of childbearing potential who do not agree to abstinence or, if sexually active, do not agree to the use of highly effective contraception
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
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. Active or systemic bacterial, fungal, or viral infection as documented by positive cultures, radiological imaging techniques, or septic shock syndrome. Such infections should have been resolved for =2 weeks before including the patient in the study
7. Impaired cardiac function as defined in the protocol
8. Patients with documented 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 is not permitted unless the patient has received imatinib for less than 2 weeks prior to the first dose of study drug and discontinued at least 5 days prior to the first dose of nilotinib.
10. Patients who have received myelosuppressive chemotherapy within 3 weeks, imatinib within 5 days, or dasatinib within 3 days prior to the 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 receiving hydroxyurea greater than 21 days for the treatment of Ph+ CML either prior to initiation of nilotinib or with maximum duration planned to exceed one week post initiation of nilotinib
13. Patients who have received hematopoietic growth factors within 7 days prior to starting study drug
14. Patients who have received Pegfilgrastim (Neulasta®) within 14 days prior to starting study drug
15. In case of Stem Cell Transplant (SCT) or Rescue without total body irradiation (TBI):
Evidence of either active graft vs. host disease or less than 3 months since SCT.
16. 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
17. Patients with known Hepatitis B, Hepatitis C, or HIV infection
18. Patients who, in the opinion of the investigator, are unlikely to comply with the protocol or safety monitoring requirements
19. Patients who are breast feeding
20. Patients who have a known hypersensitivity to the active ingredient or any of the excipients including lactose
21. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, mal-absorption, small bowel resection,

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: 19.1 Level: LLT Classification code 10009012 Term: Chronic myelogenous 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

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

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 Outcome(s)

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

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 ID(s)

2013-000200-41-IT

CAMN107A2203

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 28/08/2013
Contact: