A Phase I Study of BMS-354825 (Dasatinib) in Children With Recurrent/Refractory Solid Tumors or Imatinib Resistant Ph+ Leukemia (BMS Trial CA180038)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose defined as the maximum dose at which fewer than 1/3 patients experience dose-limiting toxicities (DLT) graded according to CTCAE
研究概览
简要总结
This phase I trial is studying the side effects and best dose of dasatinib in treating young patients with recurrent or refractory solid tumors or Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myelogenous leukemia that did not respond to imatinib mesylate. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth
详细描述
PRIMARY OBJECTIVES:
I. Determine the toxicities and estimate the maximum tolerated dose or the recommended phase 2 dose of dasatinib in pediatric patients with refractory solid tumors.
II. Determine the toxicities of dasatinib in pediatric patients with imatinib mesylate-resistant Philadelphia chromosome-positive (Ph+) leukemia.
III. Characterize the pharmacokinetics of dasatinib in pediatric patients with refractory solid tumors or imatinib-resistant Ph+ leukemia.
SECONDARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of 1 of the following:
- •Malignant extracranial solid tumor
- •Recurrent or refractory disease
- •Known bone marrow metastases* allowed
- •Imatinib mesylate-resistant Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), defined as M3 bone marrow in a patient who previously received imatinib mesylate-containing treatment regimen
- •Imatinib mesylate-resistant Ph+ chronic myelogenous leukemia (CML), as defined by any of the following:
- •Increasing WBC or platelet count while on imatinib mesylate therapy
- •Lack of any cytogenetic response after an adequate duration of imatinib mesylate therapy, as defined by 1 of the following:
- •Failed to achieve a complete hematologic response after completion of 3 months of imatinib mesylate treatment
- •Failed to achieve a partial or complete cytogenetic response (i.e., ≤ 35% Ph+ cells) after 6 months of imatinib mesylate treatment
- •Appearance of accelerated or blastic feature while on imatinib mesylate therapy
- •Reappearance of Ph+ clones after an initial complete cytogenetic response to imatinib mesylate
- •More than 30% increase in Ph+ cells in peripheral blood or bone marrow cytogenetics while on imatinib mesylate therapy
- •Imatinib mesylate intolerance, as defined by development of adverse effects requiring discontinuation of imatinib mesylate therapy
- •Measurable disease (for patients with CML or ALL)
- •Determined by hematologic, cytogenetic, and molecular studies for CML
- •Determined by bone marrow blast percentage for ALL
- •Measurable or evaluable disease (for patients with solid tumors)
- •No known curative therapy or survival-prolonging therapy with an acceptable quality of life
- •No CNS solid tumors
- •CNS-positive leukemia allowed
- •Karnofsky performance status (PS) ≥ 50% (for patients > 10 years of age)
- •Lansky PS ≥ 50% (for patients ≤ 10 years of age)
- •No evidence of graft-vs-host disease
- •Solid tumors:
- •Absolute neutrophil count ≥ 1,000/mm^3 (750/mm^3 if bone marrow infiltration)
- •Platelet count ≥ 100,000/mm^3 (transfusion independent) (50,000/mm^3 if bone marrow infiltration)
- •Hemoglobin ≥ 8.0 g/dL (red blood cell [RBC] transfusions allowed)
- •Platelet count ≥ 20,000/mm^3 (platelet transfusions allowed)
- •Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
- •Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age, as follows:
- •No greater than 0.6 mg/dL (1-23 months of age)
- •No greater than 0.8 mg/dL (2- 5 years of age)
- •No greater than 1.0 mg/dL (6-9 years of age)
- •No greater than 1.2 mg/dL (10-12 years of age)
- •No greater than 1.4 mg/dL (13 years of age and over [female])
- •No greater than 1.5 mg/dL (13-15 years of age [male])
- •No greater than 1.7 mg/dL (16 years of age and over [male])
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT ≤ 110 U/L
- •Albumin ≥ 2 g/dL
- •Normal 12-lead EKG with corrected QTc < 450 msec AND meets 1 of the following criteria:
- •Shortening fraction normal
- •Ejection fraction normal
- •No evidence of dyspnea at rest
- •No exercise intolerance
- •Pulse oximetry > 94% if there is a clinical indication for determination
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- 另有 29 项未显示
排除标准
- 未提供
研究组 & 干预措施
Stratum 1 (solid tumors)
Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
干预措施: dasatinib (Drug)
Stratum 1 (solid tumors)
Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Stratum 1 (solid tumors)
Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Stratum 2 (leukemia)
Patients receive dasatinib as in stratum 1. Cohorts of 3-12 patients receive escalating or de-escalating doses of dasatinib. The MTD is defined as the dose preceding that at which 7 of 12 patients experience DLT.
干预措施: dasatinib (Drug)
Stratum 2 (leukemia)
Patients receive dasatinib as in stratum 1. Cohorts of 3-12 patients receive escalating or de-escalating doses of dasatinib. The MTD is defined as the dose preceding that at which 7 of 12 patients experience DLT.
干预措施: pharmacological study (Other)
Stratum 2 (leukemia)
Patients receive dasatinib as in stratum 1. Cohorts of 3-12 patients receive escalating or de-escalating doses of dasatinib. The MTD is defined as the dose preceding that at which 7 of 12 patients experience DLT.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum tolerated dose defined as the maximum dose at which fewer than 1/3 patients experience dose-limiting toxicities (DLT) graded according to CTCAE
时间窗: 28 days
Time to disease progression
时间窗: Interval from enrollment to disease progression, death, occurrence of a second malignant neoplasm or last patient contact, assessed up to 1 month
Will be estimated separately for patients on the solid tumor and on the refractory Ph+ leukemia strata with the Kaplan Meier method.
次要结局
未报告次要终点