Children and Adolescents with Newly Diagnosed Chronic Phase CML or with Ph+ Leukemias Resistant to or Intolerant to Imatinib MedDRA version: 21.0 Level: PT Classification code 10034877 Term: Philadelphia chromosome positive System Organ Class: 10022891 - Investigations MedDRA version: 20.1 Level: LLT Classification code 10024329 Term: Leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: SPRYCEL®
Product Name: BMS-354825-03
Product Code: BMS-354825-03
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dasatinib
CAS Number: 863127-77-9
Concentration unit: mg milli
Sponsors
Bristol Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed 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) 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 BSA > 1.5 m2 is accepted. iii) For Cohort #2, resistance to i
Exclusion criteria
Exclusion criteria: 1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use a highly effective method to avoid pregnancy for the entire study period and for up to 1 month after the last dose of investigational product. b) Women who are pregnant or breastfeeding or likely to become pregnant 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. Subjects with CNS-1 (no detectable blast cells in a sample of cerebrospinal fluid), CNS-2 ( 5 leukemic blasts per cubic millimeter in a sample with 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. vii)Uncorrected hypokalemia or hypomagnesemia. b) Expected non-compliance to protocol schedule or unable to have regular follow-up 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. i) 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. ii) If required for control of peripheral blast cells or WBCs, 6-mercaptopurine or 6-thioguanine may be given up to 2 days before treatment start and corticosteroids or hydroxyurea can be given during the period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to estimate: - The major cytogenetic response (MCyR) rate to dasatinib therapy in children and adolescents with CP-CML subjects who prove resistant to or intolerant to imatinib. - The complete hematologic response (CHR) rate in children and adolescents with Ph+ ALL, AP-CML and BP-CML, who are resistant, intolerant to, or relapse after prior imatinib therapy. - The complete cytogenetic response (CCyR) rate to dasatinib therapy in children and adolescents with newly diagnosed CP-CML who are treatment-naive;Secondary Objective: ? To assess the safety and tolerability of dasatinib in children and adolescents treated with dasatinib for relapsed or refractory Ph+ leukemias ? To assess the safety and tolerability of dasatinib in children and adolescents with newly diagnosed Ph+ CP-CML who are treatment-naive. ? To evaluate additional measures of efficacy in children and adolescents with newly diagnosed CP-CML or subjects with relapsed or refractory Ph+ leukemias treated on a given regimen of dasatinib including: – best cytogenetic rates and hematological response rates – time to response and duration of response – disease free survival (DFS) – progression-free survival (PFS) and overall survival (OS) – rates of complete (CMR) and major (MMR) molecular response ? To describe the spectrum of the BCR-ABL mutations at baseline, at progression or end of treatment, and to explore the role of mutations as predictors of response;Primary end point(s): • Cohort #1: Major Cytogenetic Response (MCyR) rate, defined as the proportion of all treated subjects who achieve a complete or partial cytogenetic response on study. • Cohort #2: Complete Hematologic Response (CHR) rate, defined as the proportion of all treated subjects who achieve a confirmed CHR on study. • Cohort #3: Complete Cytogenetic Response (CCyR) rate, defined as the proportion of all treated subjects who achieve a CCyR on study.;Timepoint(s) of evaluation of this end point: Cohort | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): (1) To assess the safety and tolerability of dasatinib in children and adolescents treated with dasatinib for relapsed or refractory Ph+ leukemias (2) To assess the safety and tolerability of dasatinib in children and adolescents with newly diagnosed Ph+ CP-CML who are treatment-naive. (3) To evaluate additional measures of efficacy in children and adolescents with newly diagnosed CP-CML or subjects with relapsed or refractory Ph+ leukemias treated on a given regimen of dasatinib including: best cytogenetic and hematological response rates (Cohorts 1 & 3); (4) time to response and duration of response; (5) disease free survival (DFS); (6) progression-free survival (PFS) and overall survival (OS); (7) rates of complete (CMR) and major (MMR) molecular response. (8) To describe the spectrum of the BCR-ABL mutations at baseline, at progression or end of treatment, and to explore the role of mutations as predictors of response ;Timepoint(s) of evaluation of this end point: (1)/(2)/(4)/(5)/(6) Every week for the first eight weeks. Then every 3 months during the first two years. Every three months thereafter and at the end of protocol therapy. (3) Best cytogenetic response rates: every 3 months during the first 2 years, then yearly. Hematologic response rates: Cohort 1 and Cohort 3 - Every week for the first eight weeks, monthly until month 6, every 3 months thereafter. (7) Every 3 months during the first two years. Then every three months thereafter and at the end of protocol therapy (8) At baseline, every 3 months during the first two years, then at every 6 months, at progression or end of treatment | — |
Countries
Argentina, Australia, Brazil, Canada, France, Germany, India, Italy, Korea, Republic of, Mexico, Netherlands, Romania, Russian Federation, Singapore, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactEU Start Up Unit / Dept Manager
Bristol-Myers Squibb International Corporation
Outcome results
None listed