A Phase II Study of Dasatinib in Children and Adolescents with Newly Diagnosed Chronic Phase CML or With Ph+ Leukemias Resistant or Intolerant to Imatinib.
- Conditions
- MedDRA version: 21.0Level: PTClassification code: 10034877Term: Philadelphia chromosome positive Class: 100000004848MedDRA version: 20.1Level: LLTClassification code: 10024329Term: Leukemia Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]Children and Adolescents with Newly Diagnosed Chronic Phase CML or with Ph+ Leukemias Resistant to or Intolerant to Imatinib
- Registration Number
- CTIS2024-510784-36-00
- Lead Sponsor
- Bristol Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 149
Signed Written Informed Consent, Age and Sex a) Men and women, age 1 to 18 years. Women of childbearing potential (WOCBP) who are sexually active or plan to become sexually active must use two methods of contraception starting at the time of enrollment to the study, during the entire treatment period of the study and for 1 month after the last dose of investigational product to minimize the risk of pregnancy. At least one of the two methods selected must be regarded as a highly effective method of contraception as listed in the protocol section 4.2.1, Target Population a) Diagnosis: i) Cohort #1: Subjects must have Ph+ CML in CP (< 15% blasts in peripheral blood and bone marrow, < 20% basophils in peripheral blood, < 30% blasts + promyelocytes in peripheral blood and bone marrow, = 100 X 109 platelets/L unless secondary to recent treatment, No extramedullary involvement other than liver and/or spleen, Ph+ (with 9:22 translocation) demonstrated by bone marrow cytogenetics) ii) Cohort #2: Subjects must have Ph+ ALL or Ph+ AP- or Ph+ BP-CML: (1) Ph+ ALL have to be in first or subsequent relapse or fail to achieve a complete hematological remission. (2) Ph+ 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 (c) = 20% basophils in peripheral blood or bone marrow (d) < 100 X 109/L platelets unrelated to therapy (3) Ph+ 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 (< 15% blasts in peripheral blood and bone marrow, < 20% basophils in peripheral blood, < 30% blasts + promyelocytes in peripheral blood and bone marrow , = 100 X 109 platelets/L unless thrombocytopenia secondary to recent treatment, No extramedullary involvement other than liver and/or spleen, Ph+ (with 9:22 translocation) by bone marrow cytogenetics) b) Subjects in Cohort #1 or Cohort #2 have to be proven resistant or intolerant to imatinib: i)Intolerance Definition: 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 of imatinib therapy at a daily dose of 260 mg/m2 or greater. (c) Failure to achieve CCyR after = 12 months of imatinib therapy at a daily dose of 260 mg/m2 or greater. (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. 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. (d) For subj
) 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 blast cells in a sample with < 10 erythrocytes per cubic millimeter) and CNS-3 disease (> 5 leukemic blasts per cubic millimeter in a sample with < 10 erythrocytes per cubic millimeter) are eligible for study, 28 provided this is a combined relapse which also involves the bone marrow in addition to CNS and they are asymptomatic (no convulsions or other neurological symptoms). c) Isolated extramedullary disease, with < 5% blasts in bone marrow, ) Medical History and Concurrent Diseases a) Any serious uncontrolled medical disorder that would impair the XML File Identifier: z6kdvfPhIIlyNDn6+JcpAPdG1JU= Page 25/41 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 prior to inclusion is highly recommended but 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 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. 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
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