A Phase II Study of Dasatinib Therapy in Children and Adolescents with Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia or with Ph+ Leukemias Resistant or Intolerant to Imatinib Revised Protocol 02 incorporating Administrative Letter 01, 02 & Protocol Amendment 03 and 07 (04- Oct-2010)
- Conditions
- Children and Adolescents with Newly Diagnosed Chronic Phase CML or with Ph+ Leukemias Resistant to or Intolerant to ImatinibMedDRA version: 14.1Level: HLGTClassification code 10024324Term: LeukaemiasSystem Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2008-002260-33-IT
- Lead Sponsor
- Bristol-Myers Squibb Internaltional Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 145
1) Signed Written Informed Consent a) Written informed consent from subject, or from parents minor subjects, according to local law and regulation. 2) Target Population a) Diagnosis: i) Cohort #1: Subjects must have Ph+ CML in CP which 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: (1) Ph+ ALL have to be in first or subsequent relapse [defined as loss of a complete hematologic response as defined in Section 4.3.1.1] or fail to achieve a complete hematological remission [as defined in Section 4.3.1.1]. (2) 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 (3) BP-CML has to meet either of 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 iii) Cohort #3: Subjects must have been newly diagnosed with 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 b) Subjects in Cohort #1 or Cohort #2 have to be proven resistant or intolerant to imatinib: i) Intolerance Definition: Cohort #1 and Cohort #2, 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 (refer to Section 4.3.2 for CHR loss criteria). Capping the dose at 400 mg QD in chronic phase CML subjects with a BSA > 1.5 m2 is accepted. (b) Failure to achieve MCyR after `?¥ 6 months of imatinib therapy at a daily dose of 260 mg/m2 or greater. (refer to Section 4.3.1.2 for cytogenetic response definitions) Capping the dose at 400 mg QD in chronic phase CML subjects with a BSA > 1.5 m2 is accepted; (c) Failure to achieve CCyR after `?¥ 12 months of imatinib therapy at a daily dose of 260 mg/m2 or greater. (refer to Section 4.3.1.2 for cytogenetic response definitions) Capping the dose at 400 mg QD in chronic phase CML subjects with a BSA > 1.5 m2 is accepted; (d) Absolute increase of `?¥ 30% of the percentage of Ph+ metaphases, confirmed at 2 - 4 weeks, after prior MCyR to imatinib at a daily dose of 260 mg/m2 or greater. Capping the dose at 400 mg QD in chronic phase CML subjects with a BS
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 12 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) at the time when subject is assessed for enrollment b) Subjects with isolated central nervous system disease are excluded from study. This criterion relates to subjects with CNS-3 disease (`?¥ 5 leukemic blasts per cubic millimeter in a sample with < 10 erythrocytes per cubic millimeter). Subjects with CNS-1 (no detectable blast cells in a sample of cerebrospinal fluid) and CNS-2 (< 5 leukemic blast cells in a sample with < 10 erythrocytes per cubic millimeter) are eligible for study.46 Subjects with a combined relapse which also involves the CNS are eligible, provided this is asymptomatic (no convulsions or other neurological symptoms). 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 iv) Subjects diagnosed with the T315I mutation (mutation testing should be performed according to the investigator`s standard practice and is not mandatory at sites without BCR-ABL testing available). v) Subjects who have experienced hypersensitivity to dasatinib or to any of the excipients. Inactive ingredients in dasatinib tablets include: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate. The tablet coating consists of hypromellose, titanium dioxide, and polyethylene glycol. vi) Subjects with hereditary problems of galactose intolerance or Lapp lactase deficiency or glucose-galactose malabsorption. 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method