To compare the best confirmed complete cytogenetic response (CCyR) rates within 12 months in newly diagnosed chronic phase CML subjects treated with dasatinib versus imatinib
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To compare the best confirmed complete cytogenetic response (CCyR) rates within
12 months in newly diagnosed chronic phase CML subjects treated with dasatinib
versus imatinib
Secondary outcome
To compare different efficacy parameters within 12 months: major molecular
response rate, major cytogenetic response rate and complete haematologic
response.
To compare different study parameters within 12 months: best response rates
,duration of the different responses, progression free survival and time to
treatment failure.
To explore the toxicity profile for each treatment arm.
To explore the development of BCR-ABL gene mutations in each treatment arm.
Background summary
Imatinib is the current approved standard treatment for newly diagnosed CML.
However, Dasatinib has also been shown to be efficacious in subjects resistant
and intolerant to imatinib and has been approved by the FDA for treatment in
this setting. In an ongoing phase II trial in chronic phase CML subjects that
are treatment naïve, Dasatinib has been shown to produce rapid and positive
complete cytogenetic response rates. It is important to confirm these initial
results in a Phase III comparative trial. If the results from this trial are
positive for Dasatinib, it would provide improved treatment options for this
sub-set of CML patients.
Study objective
To compare the best confirmed complete cytogenetic response (CCyR) rates within
12 months in newly diagnosed chronic phase CML subjects treated with dasatinib
versus imatinib
Study design
Open label, subjects will be randomised to receive either Imatinib or
dasatinib. Randomisation will be stratified by Hasford score (refer to
protocol) and prior imatinib.
Intervention
Either dastanib (400mg QD) or imatinib (100mg QD), both orally administered.
Study burden and risks
Patients will be subject to invasive procedures (blood and bone marrow
sampling) but these procedures will be performed by trained medical staff so
any risks or pain associated with these procedures should be minimised. The
most commonly reported toxicities from either drug treatment is
myelosuppression and those as listed in section E9, some of which can be severe
in nature. However, patients will be followed closely for toxicities and
appropriate medical care given and based on previous human studies these
toxicities are manageable.
Vijzelmolenlaan 9
3440 AM Woerden
NL
Vijzelmolenlaan 9
3440 AM Woerden
NL
Listed location countries
Age
Inclusion criteria
- Subjects must have Philadephia Chromosome positive CML as defined in section 4.2.1 point 2 of the protocol.
- Subjects must be previously untreated for chronic CML (however less than 28 days of prior treatment with imatinib is allowed, refer to 4.2.1 point 3)
- Subjects must be enrolled within 90 days of diagnosis of CML, based on cytogenetic testing confirming the presence of the Philadephia Chromosome.
- ECOG performance status score 0-2
- Adequate hepatic function-refer to protocol section 4.2.1 point 6 for hepatic parameters that need to be met.
- Adequate renal function-refer to protocol section 4.2.1 point 7.
- Aged 18 years +
-Women of child bearing potential (WOCBP) are to use an adequate contraception 4 weeks before the study, throughout the study and for at least 4 weeks after discontinuing from the study.
- WOCBP must have a negative serum or urine pregnancy test within 72 hours of the start of the study drug.
Exclusion criteria
-WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy 4 weeks before the study, throughout the study and for at least 4 weeks after discontinuing from the study.
-Women who are pregnant or breastfeeding
-Women with a positive pregnancy test at enrolment or prior to study treatment
- Men whose sexual partners are WOCBP who are unwilling or unable to use an accepted method of contraception throughout the study and for at least 4 weeks after discontinuing from the study.
- A serious uncontrolled medical disorder or active infection
- Known pleural effusion at baseline
- Uncontrolled or significant heart disease (see section 4.2.2 point 8 for examples)
- History of any significant bleeding disorder unrelated to CML (see section 4.2.2 point 9 for examples).
- Prior chemotherapy for peripheral stem mobilisation
- Prior of concurrent malignancy (see exceptions in section 4.2.2 point 11)
- Evidence of digestive dysfunction that would prevent oral administration of study drug.
- Any prior treatment with interferon
- Any prior treatment with dasatinib
- Any other prior systemic treatments with anti- CML activity (see exceptions in section 4.2.2 point 15)
- Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes, refer to section 5.5.1 of the protocol.
- Prisoners or subjects who are compulsory detained for treatment of either a psychiatric or physical illness must not be enrolled.
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 |
|---|---|
| Other | Clintrials.gov and the identifier number is NCT00481247. |
| EudraCT | EUCTR2006-005712-27-NL |
| CCMO | NL18134.091.07 |