Long-Term Safety and Efficacy of Dasatinib (BMS-354825) in Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in Subjects Who Experienced Clinical Benefit on Protocol CA180-002
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 主要终点
- Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation.
研究概览
简要总结
To determine the long term safety and tolerability of dasatinib exposure in subjects previously treated in CA180-002.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent
- •Previous treatment with dasatinib on protocol CA180-002 and receiving clinical benefit in the opinion of the investigator
- •Completed a minimum of 3 months on protocol CA180-002
- •Eastern Cooperative Oncology Group (ECOG)performance status 0, 1, or 2 (See Appendix 1)
- •Prior history of Ph+ chronic, accelerated, or blast phase CML or Ph+ ALL
排除标准
- •Women of childbearing potential(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 study
- •WOCBP using a prohibited contraceptive method
- •Women who are pregnant or breastfeeding
- •Met the criteria as defined in protocol CA180-002 for discontinuation of therapy which includes:
- •Withdrawal of informed consent (subject's decision to withdraw for any reason)
- •Any clinical adverse event, laboratory abnormality or intercurrent illness which, in the opinion of the investigator, indicates that continued treatment with dasatinib is not in the best interest of the subject
- •Imprisonment or the compulsory detention for treatment of either a psychiatric or physical (e.g., infectious disease) illness
- •Medical History and Concurrent Diseases
- •A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive protocol therapy;
- •Uncontrolled angina within 3 months
- •Diagnosed or suspected congenital long QT syndrome
- •Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- •Prolonged corrected QT(QTc) interval on pre-entry electrocardiogram (> 450 msec)
- •Uncontrolled hypertension
- •Dementia or altered mental status that would prohibit the understanding or rendering of informed consent;
- •History of significant bleeding disorder unrelated to CML, including:
- •Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
- •Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
- •Physical and Laboratory Test Findings
- •Total bilirubin ≥ 1.5 mg/dl
- •alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2 times the institutional upper limits of normal
- •Serum creatinine ≥ 1.5 times the institutional upper limits of normal
- •Prohibited Therapies and/or Medications
- •Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including:
- •quinidine, procainamide, disopyramide
- •amiodarone, sotalol, ibutilide, dofetilide
- •erythromycins, clarithromycin
- •chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
- •cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
- •Medications that inhibit platelet function and any non-steroidal anti-inflammatory drug) or anticoagulants are prohibited unless a previous exception on CA180-002 was granted by the medical monitor. Subjects taking anagrelide for thrombocytosis due to CML are eligible for this protocol
研究组 & 干预措施
Dasatinib
干预措施: Dasatinib (Drug)
结局指标
主要结局
Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation.
时间窗: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.
AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to AEs were recorded. These data differ from that in the Participant Flow section. This is because the data were collected on 2 different pages of the Case Report Form and were not reconciled.
Number of Participants Who Experienced Drug-related AEs and Drug-related SAEs.
时间窗: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.
Drug-related AEs are those events with a relationship to the study therapy of certain; probable; or possible or missing. Drug-related SAEs are those events with any relationship to the study therapy.
Number of Participants With Grade 3-4 Hematology Abnormalities
时间窗: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.
Abnormalities were graded per the National Cancer Institute(NCI)Common Toxicity Criteria (CTC), v3.0(Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Hemoglobin: Grade 3:6.5 - \<8.0g/dL, Grade 4: \<6.5g/dL. Platelets: Grade 3: 25.0 - \<50.0\*10\^9/L, Grade 4: \<25.0\*10. Absolute Neutrophil Count (ANC): Grade 3: 0.5 - \<1.0\*10\^9/L, Grade 4: \<0.5\*10\^9/L.White Blood Cells (WBC) : Grade 3: 1.0 - \<2.0\*10\^9/L, Grade 4: \<1.0\*10\^9/L.
Number of Participants With Grade 3-4 Serum Chemistry Abnormalities
时间窗: From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.
Abnormalities were graded per the NCI (CTC), v3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Alanine aminotransferase (ALT): Grade 3: 5.0-20.0 \* ULN (upper limit of normal), Grade 4: \>20.0 \* ULN; Calcium: Grade 3: 6.0-\<7.0 or \>12.5-13.5 mg/dL, Grade 4: \<0.6-\>13.5 mg/dL; Bilirubin: Grade 3: \>3-10 \* ULN, Grade 4: \>10 \* ULN; Creatinine: Grade 3: \>3.0-6.0 \* ULN, Grade 4: \>6.0 \* ULN; Albumin: Grade 3: \<2g/dL (Grade 4 not defined in NCI CTC); Magnesium: Grade 3: 0.6-\<0.8 or \>2.46-6.6mEq/L, Grade 4: \<0.6 or \>6.6mEq/L.
Number of Participants With Dose Interruptions and Dose Reductions
时间窗: From start of study to final assessment (up to 32.2 months).
Dose interruptions and reductions were allowed, in order to optimize individual participant's hematologic, cytogenetic, and molecular response while maintaining and evaluating safety and tolerability of long-term exposure to dasatinib. A dose reduction is defined as the administration of a dose at a lower level compared to previous dose and such that reduced dose, or a lower dose, is given at least 4 consecutive times. In determining the reductions, dose level would be compared to the previous non-null dose. Dose interruption is defined as a complete omission of dosing for 4 consecutive times.
次要结局
- Number of Participants With Complete Hematologic Response (CHR)(Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.)
- Median Number of Months of CHR (Kaplan Meier Method)(Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.)
- Number of Participants With Major Cytogenetic Response (MCyR)(Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.)
- Median Number of Months of Major Cytogenetic Response (MCyR)(Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.)
- Number of Participants With Best Cytogenetic Response(Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.)
- Median Number of Months of Progression-free Survival (PFS) (Kaplan Meier Method)(Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.)
- Median Number of Months of Overall Survival (OS) (Kaplan Meier Method)(Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.)