To evaluate the CCyR rate at 12 months of nilotinib compared to imatinib in adult patients with Ph+ CML in CP who have a suboptimal cytogenetic response on imatinib.
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the CCyR rate at 12 months of nilotinib compared to imatinib in
adult patients with Ph+ CML in CP who have a suboptimal cytogenetic response on
imatinib.
Secondary outcome
To evaluate the rate of durable CCyR at 24 months (patients who have achieved
CCyR by 12 months, and also maintain continuous CCyR until the 24 month time
point).
To evaluate the rate of a major molecular response (MMR) of nilotinib compared
to imatinib in adult patients with Ph+ CML in CP.
To evaluate the rate of durable CCyR over the initial 24 months of this study
in adult patients with Ph+ CM in CP who have a suboptimal cytogenetic response
to imatinib. Rate of durable CCyR over 24 months is defined as the proportion
of patients who have been in continuous CCyR for a period of at least one year
during this 24 month time period.
To evaluate the CCyR rate of nilotinib compared to imatinib in adult patients
with Ph+ CML in CP at 24 months.
To evaluate the time to and duration of CCyR of nilotinib compared to imatinib
in adult patients with Ph+ CML in CP.
To evaluate the rate of a > 4 log reduction in BCR-ABL transcript levels of
nilotinib compared to imatinib in adult patients with Ph+ CML in CP.
To evaluate the time to and duration of a > 4 log reduction in BCR-ABL
transcript levels of nilotinib compared to imatinib in adult patients with Ph+
CML in CP.
To describe overall survival, progression free survival, and event-free
survival up to 5 years in adult patients with Ph+ CML in CP.
To evaluate the safety profile of nilotinib and imatinib in adult patients with
Ph+ CML in CP.
To investigate the presence of BCR-ABL mutations in patients at the initiation
of the study and during the course of treatment and correlate the mutations
with treatment response to nilotinib and imatinib.
To examine whether individual genetic variation ingenes relating to drug
metabolism,CML, and the drug target pathway confer differential response to
nilotinib and imatinib (pharmacogenetic assessment).
To identify sources of variability in PK parameters for both nilotinib and
imatinib and to investigator PK/PD relationships.
To examine the patient reported outcocmes (PRO) including quality of life (QoL)
between nilotinib and imatinib.
Background summary
Imatinib mesylate binds to the inactive conformation of BCR-ABL tyrosine kinase
suppressing the Ph+ clone in CML. It is effective in CML and is a major advance
in therapy. Evidence suggests that in individuals treated with imatinib the
achievement of a complete cytogenetic response (CCyR) is a predictor of
positive outcome. If a patient has not achieved at least a partial cyctogenetic
response (PCyR) by 12 months, achievement of CCyR is unlikely.
Nilotinib is a novel, oral tyrosine kinase inhibitor with improved potency
compared with imatinib. Niltinib was also found to have an acceptable
tolerability profile. Preliminary results from an ongoing study appear to
confirm the efficacy and safety profile of nilotinib. In this study the effect
on CCyR of nilotinib will be compared with imatinib.
Study objective
To evaluate the CCyR rate at 12 months of nilotinib compared to imatinib in
adult patients with Ph+ CML in CP who have a suboptimal cytogenetic response on
imatinib.
Study design
After the screeningperiod patients will be randomized 1:1 between nilotinib and
imatinib. Patients will be treated open label.
Patients will be treated until progressive disease, until unacceptable toxicity
or up to 5 years.
Patients who continue on study will be followed for up to 5 years for event
free, progression free, and overall survival.
Intervention
After randomization patients will be treated with imatinib 2x400 mg or
nilotinib 2x400 mg. A cycle is 28 days, patients take their medication
continuously.
Study burden and risks
After the screening period patients will visit the hospital every week first
month of treatment. Until 6 months of treatment patients will visit the
hospital every month. After 2 years of treatment patients will visit the
hospital every 3 months up to 5 years of treatment.
Evaluation of response will be determined by cytogenetics of the bone marrow
assessment.
ECG's and ECHO's are performed to monitor the cardiac function.
Possible risks for patients during the course of this study are toxicity from
nilotinib and imatinib and the effects of venapuncture and bone marrow
assessment.
Mogelijk risico gedurende dit onderzoek zijn de bijwerkingen van imatinib en
nilotinib, gevolgen van venapuntie en gevolgen van beenmergafname.
Haaksbergerstraat 55
7700 KA Enschede
NL
Haaksbergerstraat 55
7700 KA Enschede
NL
Listed location countries
Age
Inclusion criteria
Adult patients with suboptimal cytogenetic response to a dose of 400 mg imatinib (first line therapy) defined as:
* 6-12 months of treatment and have 36-95% Ph+ metaphases or
* 12-18 months of treatment and have 1-35% Ph+ metaphases;EOG 0, 1, or 2;Patients must meet the following laboratory criteria:
Total bilirubin <1.5 X ULN
SGOT and SGPT <2.5 X ULN
Creatinine <1.5 X ULN
Serum potassium, phosphorus, magnesium and calcium >LLN or correctable with supplements prior to first dose of study drug.;Written informed consent.
Exclusion criteria
Previously documented T315I mutations;Achieved prior PCyR or CCyR on imatinib and lost that response prior to entering the study;Prior treatment with > 400 mg imatinib;Previous treatment with any other tyrosine kinase inhibitor except imatinib;Impaired cardiac function
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 | EUCTR2005-005047-26-NL |
| CCMO | NL18485.044.07 |