A Dose Escalation Phase I/II Study of Clofarabine Plus Cytarabine With Growth Factor Priming in Patients Who Are Not Felt to be Candidates for More Aggressive Treatment, With Int-2 and High-Risk MDS
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose of Clofarabine (Phase I)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or in peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving clofarabine and cytarabine together with G-CSF may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and G-CSF in treating patients with myelodysplastic syndromes.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose (MTD) of clofarabine when administered with low-dose cytarabine and filgrastim (G-CSF) in patients with intermediate-2 or high-risk myelodysplastic syndromes (MDS).
- To evaluate efficacy as measured by hematologic response rates in patients who are treated with this novel combination of drugs and who are not candidates for more intensive treatment for intermediate-2 and high-risk MDS.
Secondary
- To assess effects on quality of life of this patient population.
- To assess the time to acute myeloid leukemia transformation or death.
- To assess cytogenetic response rates.
- To assess changes in flow cytometric patterns.
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
- 19 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed pathologic diagnosis of myelodysplastic syndromes
- •International Prognostic Scoring System score of intermediate-2 or high-riskFailed or progressed after 1 prior FDA-approved treatment for MDS OR refused the FDA-approved treatment
- •Not a candidate for intensive or standard chemotherapy or stem cell transplantation, as determined by the treating physician
- •ECOG performance status 0-2
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST or ALT ≤ 3 times ULN
- •Creatinine < 2.0 mg/dL
- •Fertile patients must use effective contraception
排除标准
- •Not pregnant or nursing
- •No comorbidity or condition that, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol or that would decrease life expectancy to < 3 months
- •No active, serious infection not controlled by oral or IV antibiotics
研究组 & 干预措施
Treatment
G-CSF 300 μg subcutaneously to begin one day prior to treatment and continued until ANC greater than 1.0 or recovers back to the patients baseline ANC for 3 days in a row subsequent to completion of chemotherapy (SOC) Low-dose Cytarabine 10 mg/m2 subcutaneously daily starting on day 1 for the first 5 consecutive days of the treatment course 2-4 hours following the end of the clofarabine infusion. (SOC) Clofarabine starting at dose level 0. Dose-10 mg/m2 IV over 1 hour daily starting on day 1 for the first 5 consecutive days of the treatment course The G-CSF and cytarabine doses are fixed. The dose of clofarabine is initially fixed. For the subsequent cohort, the dose of clofarabine will be advanced to the next dose level.
干预措施: filgrastim (Biological)
Treatment
G-CSF 300 μg subcutaneously to begin one day prior to treatment and continued until ANC greater than 1.0 or recovers back to the patients baseline ANC for 3 days in a row subsequent to completion of chemotherapy (SOC) Low-dose Cytarabine 10 mg/m2 subcutaneously daily starting on day 1 for the first 5 consecutive days of the treatment course 2-4 hours following the end of the clofarabine infusion. (SOC) Clofarabine starting at dose level 0. Dose-10 mg/m2 IV over 1 hour daily starting on day 1 for the first 5 consecutive days of the treatment course The G-CSF and cytarabine doses are fixed. The dose of clofarabine is initially fixed. For the subsequent cohort, the dose of clofarabine will be advanced to the next dose level.
干预措施: clofarabine (Drug)
Treatment
G-CSF 300 μg subcutaneously to begin one day prior to treatment and continued until ANC greater than 1.0 or recovers back to the patients baseline ANC for 3 days in a row subsequent to completion of chemotherapy (SOC) Low-dose Cytarabine 10 mg/m2 subcutaneously daily starting on day 1 for the first 5 consecutive days of the treatment course 2-4 hours following the end of the clofarabine infusion. (SOC) Clofarabine starting at dose level 0. Dose-10 mg/m2 IV over 1 hour daily starting on day 1 for the first 5 consecutive days of the treatment course The G-CSF and cytarabine doses are fixed. The dose of clofarabine is initially fixed. For the subsequent cohort, the dose of clofarabine will be advanced to the next dose level.
干预措施: cytarabine (Drug)
Treatment
G-CSF 300 μg subcutaneously to begin one day prior to treatment and continued until ANC greater than 1.0 or recovers back to the patients baseline ANC for 3 days in a row subsequent to completion of chemotherapy (SOC) Low-dose Cytarabine 10 mg/m2 subcutaneously daily starting on day 1 for the first 5 consecutive days of the treatment course 2-4 hours following the end of the clofarabine infusion. (SOC) Clofarabine starting at dose level 0. Dose-10 mg/m2 IV over 1 hour daily starting on day 1 for the first 5 consecutive days of the treatment course The G-CSF and cytarabine doses are fixed. The dose of clofarabine is initially fixed. For the subsequent cohort, the dose of clofarabine will be advanced to the next dose level.
干预措施: microarray analysis (Genetic)
Treatment
G-CSF 300 μg subcutaneously to begin one day prior to treatment and continued until ANC greater than 1.0 or recovers back to the patients baseline ANC for 3 days in a row subsequent to completion of chemotherapy (SOC) Low-dose Cytarabine 10 mg/m2 subcutaneously daily starting on day 1 for the first 5 consecutive days of the treatment course 2-4 hours following the end of the clofarabine infusion. (SOC) Clofarabine starting at dose level 0. Dose-10 mg/m2 IV over 1 hour daily starting on day 1 for the first 5 consecutive days of the treatment course The G-CSF and cytarabine doses are fixed. The dose of clofarabine is initially fixed. For the subsequent cohort, the dose of clofarabine will be advanced to the next dose level.
干预措施: biopsy (Procedure)
结局指标
主要结局
Maximum Tolerated Dose of Clofarabine (Phase I)
时间窗: 7 months
Maximum Tolerated Dose (MTD) is defined to be the dose cohort below which 2 out of 6 patients experience dose limiting toxicities or the highest dose cohort, if 2 limiting toxicities are not observed at any dose cohort. These will be presented as actual rates. Dose limiting toxicity (DLT) will be defined according to oncology standards based on NCI CTC version 2 grading criteria (DLT = \> grade 3 non-hematological toxicity or any \> 4 hematological toxicity that persists for more than 4 weeks and in the opinion of the investigator is felt not to be due to disease).
Presence of Hematologic Response (Phase II)
时间窗: Following phase I, responses must last at least 8 weeks.
These are measured in patients with pretreatment abnormalities defined as: Hemoglobin \< 11 g/dL or transfusion dependence \[erythroid- E\] Platelets less than 100 x 109/L or platelet-transfusion dependence \[platelet- P\] Absolute neutrophil count (ANC) less than 1.0 x 109/L \[neutrophil- N\] Pretreatment baseline measures of cytopenias are averages of at least 2 measurements (not influenced by transfusions)- at least 1 week apart.
次要结局
- Time to Acute Myelooid Leukemia Transformation or Death.(7months)
- Changes in Flow of Cytometric Patterns.(7 months)
- Assess Quality of Life(7 months)
- Cytogenetic Response Rates(7 months)