Ph+ Leukemia
Conditions
Interventions
Sponsors
Bristol-Myers Squibb
Bristol-Myers Squibb
Eligibility
Age
No minimum to 18 Years
Inclusion criteria
Inclusion criteria: Written informed consent from subject, or from parents or legal guardians for minor subjects, according to local law and regulation. Cohort #1: Subjects must have Ph+ CML in CP which is defined by the presence of all the following criteria: = 100 X 109 platelets/L unless thrombocytopenia secondary to recent treatment No extramedullary involvement other than liver or spleen Ph+ or variant must be demonstrated by bone marrow cytogenetics Cohort #2: Subjects must have Ph+ ALL or Ph+ AP- or BP-CML: Ph+ ALL have to be in first or subsequent relapse [ >= 25% blasts in bone marrow] or fail to achieve remission after imatinib AP-CML must meet at least one of the following criteria: >= 15% but = 30% blasts + promyelocytes in peripheral blood and in bone marrow (but percent alone has to be = 20% basophils in peripheral blood or bone marrow = 30% blasts in peripheral blood or bone marrow Presence of extramedullary blastic disease other than lymph nodes, liver or spleen Subjects have to be proven resistant or intolerant to imatinib: 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. For Cohort #1, resistance to imatinib must meet at least one of the following criteria: Failure to achieve, or loss of, CHR after >= 3 months of imatinib at a daily dose of 260 mg/m2 or greater; 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; 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. For Cohort #2, resistance to imatinib must meet at least one of the following criteria: 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 Subjects who achieved a CHR subsequently no longer meet the criteria consistently over a consecutive 2-week period while receiving imatinib Absolute increase of >= 30% of the percentage of Ph+ metaphases, confirmed at >= 6 week interval, after prior MCyR to imatinib. Lansky or Karnofsky scale > 50 Life expectancy >= 12 weeks 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. 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). 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 risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not unde
Exclusion criteria
Exclusion criteria: 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. Women who are pregnant or breastfeeding Women with a positive pregnancy test on enrollment or prior to investigational product administration. 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. Subjects for whom potentially-curative therapy is available, including hematopoietic stem-cell transplantation (HSCT) at the time when subject is assessed for enrollment 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 450 ms (Fridericia correction) on baseline electrocardiogram 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). 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. Subjects with hereditary problems of galactose intolerance or Lapp lactase deficiency or glucose-galactose malabsorption. Expected non-compliance to protocol schedule or unable to have regular followup due to psychological, social, familial or geographic reasons Prior therapy with dasatinib. 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. Subjects requiring ongoing medications which may: Have a known risk of causing QTc prolongation ii) Irreversibly inhibit platelet function, or anticoagulants (Does not apply to low-dose heparin for prophylaxis or to heparin flushes for i.v. lines) For Coh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary purpose of this Phase II study is to demonstrate the efficacy of dasatinib therapy in children and adolescents with newly diagnosed Chronic Phase-Chronic Myeloid Leukemia, who are treatment naive, and Chronic Phase-Chronic Myeloid Leukemia, Philadelphia chromosome positive Acute Lymphoblastic Leukemia, Accelerated Phase-CML and Blast Phase-CML who were resistant, intolerant to,or relapsed after prior imatinib therapy.;Cohort #1: Best 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Cohort #1 and Cohort #3: best CHR rates Cohort #2: best MCyR rates For all Cohorts: Rates of best cytogenetic response Duration of and time to cytogenetic and hematologic response. Progression-free Survival (PFS) and Disease free survival (DFS) Overall Survival | — |
Countries
Brazil, France, Italy, Netherlands, Russian Federation, United Kingdom, United States
Contacts
Public ContactJuliana Castro
Bristol-Myers Squibb
Outcome results
None listed