Intensified Tyrosine Kinase Inhibitor Therapy (Dasatinib NSC# 732517) in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 134
- 主要终点
- Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy
研究概览
简要总结
This phase II/III trial is studying the side effects and how well giving dasatinib together with combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia (ALL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with combination chemotherapy may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the feasibility and toxicity of an intensified chemotherapeutic regimen that incorporates dasatinib for treatment of children, adolescents, and young adults (up to age 30) with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).
II. To determine whether the intensification of tyrosine kinase inhibition through the addition of dasatinib in Induction (Days 15-28) and substitution of dasatinib for imatinib during post-Induction therapy, in the context of intensive cytotoxic therapy (according to AALL0031) and a good early response to therapy, will lead to a 3-year event-free survival (EFS) of at least 60% in patients with Ph+ ALL.
SECONDARY OBJECTIVES:
I. To determine whether the addition of dasatinib during Induction therapy (Days 15-28) will decrease levels of minimal residual disease (MRD) present at end of Induction therapy as compared with COG AALL0031.
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
- 2 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed acute lymphoblastic leukemia (ALL)
- •Definitive evidence of BCR-ABL fusion (Philadelphia chromosome positive [PH+]) from an approved Children's Oncology Group (COG) cytogenetics laboratory
- •Meets one of the following criteria:
- •Concurrent enrollment on Clusters of Orthologous Groups (COG)-AALL03B1 (or a successor trial) AND COG-AALL0232, COG-AALL0331, COG-AALL0434 or other front-line COG ALL clinical trial
- •Concurrent enrollment on COG-AALL03B1 (or a successor trial) AND scheduled to receive a 3 or 4-drug standard induction regimen
- •Concurrent enrollment on a Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium trial (or scheduled to be treated as per a DFCI Childhood ALL Consortium induction regimen)
- •All patients must have definitive evidence of BCR-ABL fusion from an approved COG cytogenetics laboratory; patients may NOT have received Day 15 of Induction chemotherapy (or day 18 vincristine if enrolled on a DFCI Childhood ALL Consortium trial) prior to enrollment on AALL0622
- •Patients must have a performance status of 0, 1 or 2 at completion of two weeks of Induction; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or maximum serum creatinine based on age and gender as follows:
- •0.4 mg/dL (for patients 1 to 5 months of age)
- •0.5 mg/dL (for patients 6 to 11 months of age)
- •0.6 mg/dL (for patients 1 year of age)
- •0.8 mg/dL (for patients 2 to 5 years of age)
- •1.0 mg/dL (for patients 6 to 9 years of age)
- •1.2 mg/dL (for patients 10 to 12 years of age)
- •1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
- •1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)
- •Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times ULN for age
- •Shortening fraction >= 27% by echocardiogram or ejection fraction >= 50% by gated radionuclide study
- •No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at sea level if there is clinical indication for determination
- •Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided
- •Patients will start AALL0622 therapy on day 15 of induction therapy (or day 18 if enrolled on a DFCI Childhood ALL Consortium trial); patients must have received the first 2 weeks of Induction therapy
排除标准
- •Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method
- •Female patients who are lactating must agree to stop breast-feeding
- •Patients with Down syndrome
- •Patients with any clinically significant cardiovascular disease including the following:
- •Myocardial infarction or ventricular tachyarrhythmia within 6 months
- •Ejection fraction less than institutional normal
- •Major conduction abnormality (unless a cardiac pacemaker is present)
研究组 & 干预措施
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Asparaginase (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Cytarabine (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Dasatinib (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Dexamethasone (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Etoposide (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Filgrastim (Biological)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Hydrocortisone Sodium Succinate (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Ifosfamide (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Leucovorin Calcium (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
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干预措施: Mercaptopurine (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
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干预措施: Methotrexate (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
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干预措施: Methylprednisolone (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
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干预措施: Pegaspargase (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
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干预措施: Prednisone (Drug)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Radiation Therapy (Radiation)
Treatment (enzyme inhibitor therapy and chemotherapy)
See Detailed Description
干预措施: Vincristine Sulfate (Drug)
结局指标
主要结局
Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy
时间窗: At 3 years
Event-Free Survival (EFS) curves will be constructed using the Kaplan-Meier life table method with standard errors computed using the method of Peto and Peto. A 1-sided 95% confidence interval for EFS will be constructed.
Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events
时间窗: Weeks 3 through 23 of treatment (From week 3 Induction through Intensification Block 1)
Number of patients in safety cohort with dose limiting toxicity (DLT)(including treatment delay)
次要结局
- Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy(At the end of induction therapy (at 5 weeks))
- Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation(At end of consolidation (at 11 weeks))
- Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib)(From the time entry on study to first event or date of last follow-up, assessed up to 7 years)