A Phase II Study of Dasatinib Therapy in Children and Adolescents with Ph+ Leukemia with Resistance or Intolerance to Imatinib.

Phase 1

• Conditions: Children and Adolescents with Ph+ Leukemia with Resistance or Intolerance to Imatinib; MedDRA version: 9.1Level: LLTClassification code 10034877Term: Philadelphia chromosome positive; MedDRA version: 9.1Level: LLTClassification code 10024329Term: Leukemia

• Registration Number: EUCTR2008-002260-33-FR
• Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-10
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 145

Inclusion Criteria

1) Signed Written Informed Consent
a) Written informed consent from subject, or from parents or legal guardians for
minor subjects, according to local law and regulation.
2) Target Population
a) Diagnosis:
i) Cohort #1: Subjects must have Ph+ CML in CP which is defined by the
presence of all the following criteria:
(a) < 15% blasts in peripheral blood and bone marrow
(b) < 20% basophils in peripheral blood
(c) < 30% blasts + promyelocytes in peripheral blood and bone marrow
(d) = 100 X 109 platelets/L unless thrombocytopenia secondary to recent
treatment
(e) No extramedullary involvement other than liver or spleen
(f) Ph+ or variant must be demonstrated by bone marrow cytogenetics
ii) Cohort #2: Subjects must have Ph+ ALL or Ph+ AP- or BP-CML:
i. Ph+ ALL have to be in first or subsequent relapse [ = 25% blasts in bone
marrow] or fail to achieve remission after imatinib
ii. AP-CML must meet at least one of the following criteria:
(a) = 15% but < 30% blasts in peripheral blood or bone marrow
(b) = 30% blasts + promyelocytes in peripheral blood and in bone marrow
(but percent alone has to be < 30%)
(c) = 20% basophils in peripheral blood or bone marrow
(d) < 10 X 109/L platelets unrelated to therapy
iii. BP-CML has to meet all the following criteria:
(a) = 30% blasts in peripheral blood or bone marrow
(b) Presence of extramedullary blastic disease other than lymph nodes,
liver or spleen
b) Subjects have to be proven resistant or intolerant to imatinib:
i) For both cohorts, intolerance to imatinib is defined as the occurrence of any
toxicity grade = 3 considered at least possibly related to imatinib and that led
to discontinuation of previous imatinib therapy.
ii) For Cohort #1, resistance to imatinib must meet at least one of the following
criteria:
(a) Failure to achieve, or loss of, CHR after = 3 months of imatinib at a
daily dose of 260 mg/m2 or greater;
(b) Failure to achieve MCyR after = ?6 months or CCyR after = 12 months
of imatinib therapy at a daily dose of 260 mg/m2 or greater;
(c) Absolute increase of = 30% of the percentage of Ph+ metaphases,
confirmed at = 6 week interval, after prior MCyR to imatinib at a daily
dose of 260 mg/m2 or greater.
iii) For Cohort #2, resistance to imatinib must meet at least one of the following
criteria:
(a) Failure to achieve CHR while on imatinib after a = 4-week treatment
or a = 50% increase in peripheral blood blasts over a 2-week period
(b) Subjects who achieved a CHR subsequently no longer meet the criteria
consistently over a consecutive 2-week period while receiving imatinib
(c) Absolute increase of = 30% of the percentage of Ph+ metaphases,
confirmed at = 6 week interval, after prior MCyR to imatinib.
c) Lansky or Karnofsky scale > 50 (see Appendix 2)
d) Life expectancy = 12 weeks
e) 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.
f) Serum Na, K, NaHC03, Mg, P and Ca levels within institutional normal limits
and AST, ALT, bilirubin, BUN or urea, creatinine = Grade 2 (NCI CTCAE,
Version 3.0).
3) Age and Sex
a) Men and women, age = 1 to < 21 years
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 4 weeks after
the last dose of investigational product in such a manner that the

Exclusion Criteria

1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 4 weeks after the last dose of
investigational product.
b) Women who are pregnant or breastfeeding
c) Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
d) Sexually active fertile men not using effective birth control if their partners are
WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 4 weeks after the last dose of
investigational product.
2) Target Disease Exceptions
a) Subjects for whom potentially-curative therapy is available, including
hematopoietic stem-cell transplantation (HSCT)
b) Symptomatic central nervous system (CNS) involvement (except if signs and
symptoms are from isolated leptomeningeal disease)
c) Isolated extramedullary disease, with < 5% blasts in bone marrow
3) Medical History and Concurrent Diseases
a) Any serious uncontrolled medical disorder that would impair the ability of the
subject to receive protocol therapy, including:
i) Ongoing uncontrolled infection
ii) Clinically-significant disorder of platelet function (e.g. von Willebrand’s
disease) or ongoing gastrointestinal bleeding
iii) Clinically-significant cardiovascular disease, congenital long QT syndrome,
history of ventricular arrhythmias or heart block, or prolonged QTc interval >
450 ms (Fridericia correction) on baseline electrocardiogram
b) Expected non-compliance to protocol schedule or unable to have regular followup
due to psychological, social, familial or geographic reasons
4) Prohibited Treatments and/or Therapies
a) Prior therapy with dasatinib.
b) 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.
c) Subjects requiring ongoing medications which may:
i) Have a known risk of causing QTc prolongation - see Section 5.5.3.2
ii) Irreversibly inhibit platelet function, or anticoagulants - see Section 5.5.3.3
(Does not apply to low-dose heparin for prophylaxis or to heparin flushes for
i.v. lines)
5) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified