An Open-Label Phase II Dose Optimization Study of Bosutinib at a Starting Dose of 300 Mg Daily for Adult Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase Post Frontline TKI Failure
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Response Rate
研究概览
简要总结
This phase II trial studies how well bosutinib works in treating patients with chronic myeloid leukemia in chronic phase after frontline tyrosine kinase inhibitor (TKI) failure. Bosutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To assess the response rate within 24 weeks in patients in chronic phase receiving bosutinib with the starting dose of 300 mg per day, with potential escalation to 400 mg, 500 mg and 600 mg per day.
SECONDARY OBJECTIVES:
I. Safety of dosing schedule. II. Frequency of treatment interruptions and dose reductions. III. Determine the rate of BCR-ABL/ABL < 10% at 3 months and < 1% at 6 months on the international scale and the rate of complete cytogenetic response (CCyR) at 6 months after the start of treatment.
IV. Determine the cumulative rate of CCyR. V. Determine the rate of major molecular response, molecular response (MR)4, MR4.5 and complete molecular response.
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
- •Patients with chronic myeloid leukemia (CML) in chronic phase who have resistance and/or intolerance to frontline TKI therapy; resistance is defined as lack (lack defined as response not achieved or lost by the given dates mentioned hereafter) of CHR (complete hematologic response) within 3 months, lack of major cytogenetic response (MCyR) within 6 months, and lack of CCyR within 12 months of therapy with frontline TKIs; in addition, loss of MCyR, CCyR or MMR at any time during the course of therapy is also considered resistance to therapy; intolerance is defined as persistent or severe toxicity that is unacceptable to the patient
- •Chronic phase disease is defined as:
- •< 15% blasts in peripheral blood and bone marrow;
- •< 30% blasts plus promyelocytes in peripheral blood and bone marrow;
- •< 20% basophils in peripheral blood;
- •>= 100 x 10^9/L platelets (>= 100,000/mm^3);
- •No evidence of extramedullary disease except hepatosplenomegaly; and
- •No prior diagnosis of accelerated phase (AP) or blastic phase-chronic myeloid leukemia (BP-CML); patients with clonal evolution but no other criteria for accelerated phase are eligible
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Creatinine less than or equal to 2.0 mg/dl
- •Bilirubin less than or equal to 2.0 mg/dl
- •Alanine aminotransferase (ALT) less than or equal to 3 times institutional upper limit of normal
- •Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include:
- •Birth control pills, shots or implants (placed under the skin by a health care provider) or patches (placed on the skin);
- •Intrauterine devices (IUDs);
- •Condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy
- •Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
- •Patients or their legally authorized representative must provide written informed consent
排除标准
- •Women who are pregnant or lactating
- •Known to be human immunodeficiency virus (HIV)+
- •Active and uncontrolled disease/infection that in the opinion of the treating physician and principal investigator may affect the ability to participate in the trial or put the patient at unduly high risk
- •Unable or unwilling to sign the informed consent document
- •Received no other investigational therapy within the past 14 days
- •Presence of T315I mutation by ABL1 sequencing
- •Patient is currently in complete cytogenetic remission (CCyR)
研究组 & 干预措施
Treatment (bosutinib)
Patients receive bosutinib PO daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Bosutinib (Drug)
Treatment (bosutinib)
Patients receive bosutinib PO daily on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Response Rate
时间窗: Up to 6 months
Response is defined as follows: 1) For patients who do not currently have a partial cytogenetic response (PCyR), achievement of major cytogenetic response is considered a response. 2) For patients who are currently in PCyR, achievement of CCyR is considered a response. The Simon's optimal two-stage design will be used for interim futility monitoring. Will be estimated along with the 95% credible interval.
次要结局
- Rates of BCR-ABL/ABL <10%(At 3 months)
- Transformation-free Survival(Up to 2 years)
- Rates of Major Molecular Response (MR), MR4, MR4.5 and Complete Molecular Response(Up to 2 years)
- Overall Survival(Up to 2 years)
- Event-free Survival(Up to 2 years)
- Change of ABL Kinase Domain Mutation Status(Baseline up to 2 years)
- Number of Participants With Treatment Interruptions and Dose Reductions(Up to 2 years)
- Rates of BCR-ABL/ABL < 1%(At 6 months)