An Open Label, Observational Clinical Study to Assess Long-term Feasibility of Reduced Dose Dasatinib in Chronic Phase Chronic Myeloid Leukemia Patients Who Have Any Grade of Adverse Events and Early Molecular Response Within 3 Months of Frontline Dasatinib Therapy
试验速览
- 阶段
- 不适用
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Rate of MMR
研究概览
简要总结
This study is conducted in patients with newly diagnosed CP CML (Chronic Phase Chronic Myeloid Leukemia) who have achieved EMR (< 10% IS BCR-ABL) at 3 months after first line treatment with dasatinib. Subjects will be allocated to 80mg QD based on EMR (Early Molecular Response) achievement and early safety profile following a standard of care approach.
详细描述
Patients will sign the consent forms for screening prior to frontline dasatinib therapy (1st) and the 3 month molecular test date (2nd). The molecular samples will be analyzed in the central lab as part of the screening procedure.
Subjects will be treated for a maximum of 60 months after allocation of the last subject on the assigned regimen (dasatinib 80mg QD), unless disease progression, treatment failure or unacceptable toxicity occurs, the subject withdraws consent, or the study is discontinued by the sponsor. Subjects who discontinue study therapy early due to disease progression or intolerance to study medication will continue to be followed yearly for survival for up to 5 years after allocation of the last subject. All subjects will be followed yearly for progression-free survival and overall survival.
For patients who continue their assigned treatment, safety assessments will be conducted every 6 months and cytogenetic assessment as investigator assessment.
Follow up visits after the last dose of study drug will be required at least every 4 weeks until all study related toxicities resolve to baseline (or CTC Grade ≤ 1), stabilize or are deemed irreversible.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Adult CML-CP Ph+ (Philadelpia) patients with BCR-ABL1 patients diagnosed within 3 months
- •Adequate renal function defined as serum creatinine ≤ 3 times the institutional ULN(Upper limit of normal)
- •Adequate hepatic function defined as: total bilirubin ≤ 2 times the institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the institutional upper limit of normal (ULN).
- •Adequate cardiac function (see exclusion criteria)
- •Adequate pulmonary function (see exclusion criteria)
- •Serum Na, K, Mg, and total serum Ca or ionized Ca levels must be greater than or equal to the institutional lower limit of normal. Subjects with low K, Mg levels, total serum Ca and/or ionized Ca must be replete to allow for protocol entry: Rescreening is permitted in the event of temporary biochemical abnormalities
- •CML-CP Ph+ patients with CHR but with BCR-ABL level < 10% IS after 3 months of frontline dasatinib 100 mg treatment. And currently persisting any grade adverse events to dasatinib 100 mg QD
- •ECOG(Eastern Cooperative Oncology Group) performance status 0-2
- •Women must not be pregnant
排除标准
- •Previous diagnosis of accelerated phase or blast crisis
- •Documented any major ABL1 mutation
- •A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive dasatinib
- •Pulmonary arterial hypertension
- •Congenital bleeding disorders
- •Prior or concurrent malignancy, except for the following
- •Subject with any anti-CML other than dasatinib
- •Subjects with prior stem cell transplantation and/or high dose chemotherapy for CML
- •Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes
- •Subjects who were previously treated with over 100mg at second phase screening
- •Subjects who are not tolerable to 80mg at second phase screening
- •Patients who are pregnant or breast feeding or likely to become pregnant
- •Prisoners or subjects who are involuntarily incarcerated
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
结局指标
主要结局
Rate of MMR
时间窗: 12 month
Level of Bcr-Abl transcript (Conventional Q-RT-PCR)
次要结局
- To assess: Number and percentage of participants with treatment-related adverse events as assessed by CTCAE v4.0.(12 months)
- MMR and MR4.5 rates by 5 years(5 years)
研究者
Dong-Wook Kim
Director
Seoul St. Mary's Hospital