Primary objectives:* To assess efficacy of nilotinib in pediatric patients with Ph+ CML CPresistant or intolerant to either imatinib or dasatinib.* To assess efficacy of nilotinib in pediatric patients with Ph+ CML APresistant or intolerant to…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Rate of MCyR by 6 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 6 months
Secondary outcome
* 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)
* Safety and tolerability: incidence and severity of adverse events, as
assessed by patient symptoms, physical exam assessments, abnormal laboratory
tests, echocardiograms and electrocardiograms
* Mutational assessments of BCR-ABL
* Questionnaire on acceptability (including palatability) of dose forms used
after first dose, cycle 1 and cycle 12
Background summary
The purpose of the phase II study is to characterize efficacy, safety and PK
parameters of nilotinib in the Ph+ CML pediatric patient population
(from 1 to <18 years). The rationale for the development of nilotinib in
pediatric Ph+ CML is that nilotinib has shown a positive benefit/risk profile
in both adult patients with Ph+ CML in CP or AP resistant or intolerant to
prior therapy including imatinib and adult patients with newly diagnosed
Ph+ CML CP.
Study objective
Primary objectives:
* 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.
Secondary objectives:
* 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-.* To assess long term effect on growth, development and
maturation of nilotiib treatment in pediatric patients with Ph+CML.
Study design
This is a multi-center open label, non-controlled study of nilotinib. Nilotinib
will be administered at 230 mg/m2 p.o., twice daily, rounded to the nearest 50
mg dose (to a maximum dose of 400mg) for up to 66 cycles (1 cycle is 28 days).
Intervention
Children will be treated with oral nilotinib long as they will benefit from it.
Response assessment every 28 days.
Study burden and risks
Risk:
Side effects of the study medication (see also the dose-limiting toxicities
described on page 34, Table 6-2), drawing blood samples and tissue biopsies.
Het collection of blood can cause a bruise, bleeding at the site or blood
clothing. These usually disappear naturally.
Burden:
-study visits at least 1 time per 28 days for 2 years after proceeding though
the screening.
-blood draws for lab tests every visit.
-other assesments such as tissue biospies and ECGs
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
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.
Exclusion 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 in less than 3 months since the last Stem Cell Transplant;7. Total body irradiation (TBI) or craniospinal radiation therapy in < 6months. Hypersensitivity to the active ingredient or any of the excipients including lactose;Additional exclusion criteria are defined in the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000200-41-NL |
| CCMO | NL45150.078.13 |