Clinical trial NCT01077544: A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Myeloid Leukemia
Acute Lymphoblastic Leukemia
Keywords: Chronic Myeloid Leukemia
Acute Lymphoblastic Leukemia
Ph+ CML
Ph+ ALL
pediatric
nilotinib
imatinib
chronic phase
accelerated phase
newly diagnosed Ph+ CML
dasatinib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-03-01
Enrollment: 15
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess the pharmacokinetics of nilotinib in Ph+ CML pediatric patients that are newly diagnosed or resistant or intolerant to imatinib or dasatinib or refractory or relapsed Ph+ ALL compared to the adult populations. It will also evaluate safety and activity of nilotinib as secondary objectives.


Eligibility criteria: Inclusion Criteria:

* Must have one of the following: newly diagnosed CP Ph+CML, CP or AP resistant/ intolerant to imatinib and/or dasatinib, or Ph+ ALL either relapsed after or refractory to standard therapy
* adequate renal, hepatic and pancreatic function

Exclusion Criteria:

* patients receiving therapy with strong CYP3A4 inhibitors and/or inducers and treatments cannot be stopped or changed to a different medication at least 14 days prior to starting study drug
* patients receiving therapy with any medications with 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.
* gastrointestinal impairment or disease that may interfere with drug absorption
* liver, pancreatic or severe renal disease unrelated to disease under study
* impaired cardiac function
* patients who received dasatinib within 3 days of starting study drug
* patients who received imatinib within 5 days of starting study drug
* patients receiving hydroxyurea or corticosteroids that has not been discontinued at least 1 week after initiation of nilotinib
* patients who received hematopoietic growth factors within 7 days of starting study drug or Pegfilgrastim (Neulasta®) within 14 days of starting study drug
* patients with Stem Cell Transplant (SCT) or Rescue without TBI: Evidence of active graft vs. host disease and \< 3 months since SCT

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Summary of Nilotinib Non-compartmental PK Parameters: Cmax
timeFrame: Cycle 1 Day 1
measure: Summary of Nilotinib Non-compartmental PK Parameters: Tmax
timeFrame: Cycle 1 Day 1
measure: Summary of Nilotinib Non-compartmental PK Parameters: AUClast (Last = 24h)
timeFrame: Cycle 1 Day 1
measure: Summary of Nilotinib Non-compartmental PK Parameters: AUC0-12h
timeFrame: Cycle 1 Day 1
measure: Summary of Nilotinib Steady-state PK Parameters: AUCss
timeFrame: Cycle 1 Day 8 - Cycle 1 Day 28
measure: Summary of Nilotinib Steady-state PK Parameters: CLF (Body Surface Area (BSA) Adjusted)
timeFrame: Cycle 1 Day 8 - Cycle 1 day 28
measure: Summary of Nilotinib Steady-state PK Parameters: Cmin
timeFrame: Cycle 1 Day 8 - Cycle 1 Day 28
Secondary outcomes:
measure: Number of Ph+ CML Participants With Confirmed Complete Hematologic Response (CHR)
timeFrame: minimum of 12 cycles (28 days per cycle)
measure: Number of Ph+ CML Participants With Cytogenic Response
timeFrame: minimum of 12 cycles (28 days per cycle)
measure: Number of Ph+ CML Participants With Major Molecular Response (MMR)
timeFrame: minimum of 12 cycles (28 days per cycle)
measure: Efficacy Endpoints for Ph+ ALL Patients
timeFrame: minimum of 12 cycles (28 days per cycle)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Novartis Investigative Site
state: Aquitaine
city: Lille cedex
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: West Midlands
country: United Kingdom
facility: Novartis Investigative Site
state: Birmingham
city: Sutton
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: