A multi-center, open-label, pharmacokinetic study of oral nilotinib in pediatric patients with newly diagnosed chronic phase (CP) Ph+ CML, with CP or accelerated phase (AP) Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or with refractory/relapsed Ph+ ALL.
- Conditions
- pediatric patients with newly diagnosed chronic phase (CP) Ph+ CML, with CP or accelerated phase (AP) Ph+ CML imatinib resistant / intolerant to imatinib and/or dasatinib, or with Ph+ CML chronic phase (CP) or accelerated phase (AP) or with refractory / relapsed Ph+ ALL.MedDRA version: 14.1 Level: LLT Classification code 10009700 Term: CML System Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2010-018419-14-GB
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
1.Male or female patients less than 18 years and more than 1 year of age at study entry.
2.Written informed consent, according to local guidelines, signed by the patients and / or by the parents or legal guardian prior to any study
related screening procedures are performed.
3.Patients must have one of the following: newly diagnosed CP Ph+
CML,or CP or AP Ph+ CML resistant/ intolerant to imatinib and/or
dasatinib, or Ph+ CML CP or AP or Ph+ ALL either relapsed after or
refractory to standard therapy.
a. Imatinib or dasatinib resistance in Ph+ CML is defined as:
• Increasing WBC or platelet count while on imatinib or dasatinib
therapy indicative of a hematological relapse or primary resistance to
imatinib or dasatinib.
• Cytogenetic or molecular response consistent with suboptimal
response or failure criteria adapted from ELN (European Leukemia Net)
recommendations
• Progression to accelerated phase or blast crisis while on imatinib or
dasatinib therapy.
• Reappearance of Ph+ bone marrow cells after a complete cytogenetic
response to imatinib or dasatinib.
• A greater than 30% increase in Ph+ cells in peripheral blood or on
bone marrow cytogenetics while on imatinib or dasatinib therapy.
• Loss of molecular response on imatinib or dasatinib therapy.
b. Imatinib/dasatinib intolerance (at any dose or duration) is defined as
the development of AEs requiring discontinuation of imatinib or
dasatinib therapy.
c. Newly diagnosed CP Ph+ CML is defined as:
• Patients with Ph+ CML-CP within 6 months of diagnosis (date of initial
diagnosis is the date of first cytogenetic analysis).
• Diagnosis of chronic myelogenous leukemia in chronic phase with
cytogenetic confirmation of Philadelphia chromosome with
(9;22)translocation (to confirm the presence of BCR-ABL and review of a
minimum 20 metaphases is required). Standard conventional
cytogenetic analysis must be done on bone marrow. FISH cannot be used for study purposes.
4. Performance status: Karnofsky = 50% for patients > 10 years of age,
and Lansky = 50 for patients = 10 years of age.
5. Patients must have adequate renal, hepatic and pancreatic function
defined as:
• Creatinine clearance or radioisotope GFR ‡ 70 ml/min/1.73 m2, or a
serum creatinine based on age
Total bilirubin (sum of conjugated + unconjugated) £ 1.5 x upper limit of normal (ULN) for age.
• Serum amylase and lipase = 1.5 x ULN
• SGPT (ALT) and SGOT (AST) £ 2 x upper limit of normal (ULN) for age.
6. Female patients of childbearing potential who agree to abstinence or,
if sexually active, agree to the use of contraception.
7. Patients must have the following laboratory values (=LLN (lower limit
of normal)) or corrected to within normal limits with supplements prior
1.Patients actively receiving therapy with strong CYP3A4 inhibitors and inducers and the treatment cannot be either discontinued or switched to a different medication at least 14 days prior to starting study drug.
2.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/printable-drug-list.cfm.
3.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, or gastric bypass surgery).
4.Acute or chronic liver, pancreatic or severe renal disease considered unrelated to CML or ALL.
5.History of pancreatitis within 12 months of starting study drug or past medical history of chronic pancreatitis.
6.No active or systemic bacterial, fungal, or viral infection as
documented by positive cultures, radiological imaging techniques, or
septic shock syndrome.
7.Impaired cardiac function including any one of the following:
•Inability to determine the QT interval on ECG
•Complete left bundle branch block
•Use of a ventricular-paced pacemaker
•Congenital long QT syndrome or a known family history of long QT syndrome.
•History of or presence of clinically significant ventricular or atrial tachyarrhythmias
•Clinically significant resting brachycardia (<50 beats per minute)
•QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
•History of clinically documented myocardial infarction within 12 months of starting study drug.
•History of unstable angina within 12 months of starting study drug.
•Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension).
8.Patients who have received dasatinib therapy within 3 days of starting study drug.
9.Patients who have received imatinib therapy within 5 days of starting study drug.
10.a)Patients who have received myelosuppressive chemotherapy within 14 days prior to first dose of study drug.
b)Patients who have not recovered from all acute toxicities from all prior myelosuppressive chemotherapy to = Grade 1 prior to starting study drug.
11. Patients receiving greater than 14 days of hydroxyurea for the treatment of Ph+ CML or corticosteroids for the treatment of Ph+ ALL and has not been discontinued at least one week after the initiation of nilotinib (see Section 6.6.4 for details on permitted concomitant use of hydroxyurea and corticosteroids).
12. a) Patients who have received hematopoietic growth factors within 7 days of starting study drug
b) Patients who have received Pegfligrastim (Neulasta®) within 14 days of starting study dru
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method