The main objective of this study is to estimate the rate of response to dasatinib in children and adolescents with certain types of Ph+ leukaemia either whose disease is resistant to, intolerant to or relapsed after previous imatinib therapy or are…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to estimate the rate of response to
dasatinib in children and adolescents with certain types of leukaemia, whose
disease is either resistant to, intolerant to, or relapsed after previous
imatinib therapy or are newly diagnosed and treatment naïve.
Secondary outcome
The secondary objectives of this study are: to assess safety and tolerability
in the above patient groups; to evaluate additional measures of
response/effectiveness: best cytogenetic and haematological response rates;
time to response; duration of response; progression-free survival; overall
survival; rates of complete and major molecular response (response at the DNA
level); to look at Bcr-abl mutations at baseline, at progression or end of
treatment and to explore the role of mutations as predictors of response.
Background summary
Dasatanib targets leukaemias that carry a genetic defect commonly known as the
'Philadelphia chromosome'. These types of leukaemias can be difficult to cure
and are known to become resistant to the currently available treatment drug,
called imatinib. Adult studies and preliminary results from studies in children
have shown dasatanib can be effective in treating this type of leukaemia. This
study will aim to find out if dasatanib is effective for this group of patients
in a larger, more statistically valid, number of patients. It will also look at
whether dasatinib is effective in newly diagnosed, treatment naïve children and
adolescents with chronic phase CML for whom immediate hematopoetic stem cell
transplant (HSCT) is not available. An additional 30 newly diagnosed patients
will be included to test the new dasatinib powder for oral suspension (PFOS).
Study objective
The main objective of this study is to estimate the rate of response to
dasatinib in children and adolescents with certain types of Ph+ leukaemia
either whose disease is resistant to, intolerant to or relapsed after previous
imatinib therapy or are newly diagnosed and treatment naïve.
Study design
Open*label, non-randomised Phase II multi*centre study in children and
adolescents with Ph+ leukaemia with either resistance or intolerance to the
standard treatment Imatinib or newly diagnosed and treatment naïve.
Patients will either receive dasatinib orally on a daily basis or in solution
form (PFOS) for as long as they are receiving benefit. Approximately 139
patients will be enrolled in total, 30 newly diagnosed patients will receive
PFOS.
Intervention
Cohort 1: Dasatinib 60mg/m2 orally once daily
Cohort 2: Dasatinib 80mg/m2 orally once daily
Cohort 3a: Dasatinib 60mg/m2 orally once daily
Cohort 3b: Dasatinib 72mg/m2 in solution form once daily
Patients in Cohorts 1,2 and 3a remaining on study can choose to be switched to
the solution form at a dose of 72mg/m2 if on the 60mg/m2 oral dose or 96mg/m2
if on the 80mg/m2 oral dose.
Study burden and risks
Dasatinib has been shown to be well tolerated in adults and children, with a
high efficacy in adult Ph+ disease. It has also shown efficacy in a few
paediatric studies with preliminary analysis showing better tolerability in
children. In light of the high efficacy in adults and favourable safety profile
seen so far in children, together with the urgent need to identify new
effective treatments for these high risk subjects, the risk:benefit ratio is
considered to be very favourable.
Uxbridge Business Park - Sanderson Road Unit 2
Uxbridge UB8 1DH
GB
Uxbridge Business Park - Sanderson Road Unit 2
Uxbridge UB8 1DH
GB
Listed location countries
Age
Inclusion criteria
1. Diagnosis:
Cohort 1: Subjects must have Ph+ CP-CML
Cohort 2: Subjects must have Ph+ ALL or Ph+ AP- or BP-CML
Cohort 3a: newly diagnosed treatment-naive chronic phase chronic myelogenous
leukemia (CP-CML)
Cohort 3b: sub-cohort of 30 newly diagnosed treatment-naive chronic phase
chronic myelogenous leukemia (CP-CML), who will receive dasatinib powder for
oral suspension (PFOS), Subjects in Cohorts 1 and 2 must have proven resistance
or intolerance to imatinib
(2) Lansky or Karnofsky scale > 50
(3) Life expectancy * 12 weeks
(4) Subjects must have recovered to baseline or Grade 1 (NCI CTCAE, version
3.0) from the toxicities (except alopecia) resulting from recent therapies,
including chemotherapy, hormonal therapy, immunotherapy, biological therapy or
investigational product and radiation therapy
(5) Serum Na, K, Na, HC03, Mg, P and Ca levels within institutional normal
limits and AST, ALT, bilirubin, serum creatinine * Grade 2 (NCI CTCAE, Version
3.0)
Exclusion criteria
(1) Subjects for whom potentially-curative therapy is available, including
hematopoietic stem-cell transplantation (HSCT)
(2) Symptomatic central nervous system (CNS) involvement (except if signs and
symptoms are from isolated leptomeningeal disease)
(3) Isolated extramedullary disease, with < 5% blasts in bone marrow
(4) Any serious uncontrolled medical disorder that would impair the ability of
the subject to receive protocol therapy
(5) Prior therapy with dasatinib
(6) Any investigational agent or any other anti-cancer agent within 14 days
prior to treatment start. Imatinib mesylate may be continued up to 7 days
before treatment start, or, in the presence of rising peripheral blast cells,
imatinib may be continued up to 2 days before treatment start. If required for
control of peripheral blast cells, hydroxyurea, corticosteroids,
6-mercaptopurine or 6-thioguanine may be given up to 2 days before treatment
start.
(7) Subjects requiring ongoing medications which may:
-Have a known risk of causing QTc prolongation
-Irreversibly inhibit platelet function, or anticoagulants (Does not apply to
low-dose heparin for prophylaxis or to heparin flushes for i.v. lines)
(8) Sexually active females of child-bearing potential that are unwilling or
unable to use an acceptable method to avoid pregnancy.
(9) Sexually active fertile malesnot using effective birth control, if their
partners are of child-bearing potential.
(10) Cohort 3a and b: no prior chemotherapy, immunotherapy, or radiotherapy for
CML with the exception of hydroxyurea
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 | EUCTR2008-002260-33-NL |
| ClinicalTrials.gov | NCT00777036 |
| CCMO | NL28377.078.09 |