NCT00531232已完成2 期
A Phase IIa Open-label, Dose Confirmation Study of Oral Clofarabine in Adult Patients Previously Treated for Myelodysplastic Syndromes (MDS)
Genzyme, a Sanofi Company6 个研究点 分布在 1 个国家目标入组 38 人开始时间: 2007年5月7日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 6
- 主要终点
- Percentage of Participants With Overall Response
研究概览
简要总结
There was no well accepted standard of care for participants who failed or were intolerant to any of the currently approved therapies for myelodysplastic syndromes (MDS). In this study, participants were initially assigned to receive 55 or 35 milligrams (mg) of oral clofarabine daily for 5 days. After safety review of the first participants enrolled, the dose was reduced to 25 milligrams per day (mg/day) for up to 8 cycles as long as the participants continued to benefit and in the absence of progressive disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Had a pathologically confirmed secondary Acute Myeloid Leukemia ([sAML]; following a history of MDS) or MDS with an intermediate-1 (with marrow blasts greater than or equal to [>=] 5%) or intermediate-2 or high risk score as assessed by the International Prognostic Scoring System at study entry. Participants with refractory anemia with excess blasts in transformation recognized by the French-American-British system, and chronic myelomonocytic leukemia were allowed into the study. Pathologic confirmation was the responsibility of the site investigator.
- •Had previously treated MDS defined as follows: a) Participants must had at least one, but no more than two, prior treatment regimens [a.) treatment regimen was defined as any drug or drug combination administered for treatment of MDS with the intent of inducing at least hematologic improvement (consistent with International Working Group criteria); Inadequate treatment, due to drug intolerance or other factors, was considered a prior treatment regimen. Hematopoietic growth factors, hydroxyurea, anti-thymocyte globulin, or supportive care measures (e.g., blood transfusions, immunosuppressive agents, antibiotics) were not considered treatment regimens for the purpose of study entry.] b.) One of the treatment regimens had to be either 5-azacytidine or decitabine. If 5-azacytidine or decitabine was given as a treatment regimen more than once, it was considered as 2 different treatment regimens. c.) Participants could not be refractory (i.e., progression of disease, or no evidence of response, while on the treatment) to more than one prior treatment regimen (to be considered refractory to decitabine or 5-azacitidine, participants must have received >= 4 cycles).
- •Had documentation of prior transfusion requirements for the preceding 8 weeks (8 weeks prior to first dose of study drug).
- •Had Eastern Cooperative Oncology Group performance status 0-
- •Was able to comply with study procedures and follow-up examinations.
- •Had adequate renal and hepatic functions as indicated by predefined laboratory values: a.) Total bilirubin less than or equal to (<=) 1.5 * institutional Upper Limit of Normal (ULN) except for unconjugated hyperbilirubinemia secondary to treatment for MDS or Gilbert's syndrome; and b.) Aspartate aminotransferase and Alanine aminotransferase <= 2.5*ULN; and c.) Serum creatinine <= 1.0 milligrams per deciliter, then the estimated glomerular filtration rate (GFR) had to be greater than (>) 30 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation.
- •Was non-fertile or agreed to use birth control during the study through the end of last treatment visit and at least 90 days after.
排除标准
- •Had an adjustment of dose and/or schedule of erythropoietin, granulocyte colony stimulating factor or other growth factors within 8 weeks prior to the first dose of oral clofarabine.
- •Had any prior therapy for treatment of sAML. Hydroxyurea must not have been received within 24 hours prior to first dose of study drug.
- •Had any other chemotherapy or any investigational therapy within four weeks of first dose of study drug.
- •Had any prior pelvic radiotherapy.
- •Had a prior hematopoietic stem cell transplant for MDS.
- •Had not recovered to <= Grade 2 from any drug-related non-hematologic toxicity prior to first dose of the study drug.
- •Had an uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- •Had a psychiatric disorder that would interfere with consent, study participation, or follow-up.
- •Had any other severe concurrent disease, or had a history of serious organ dysfunction or disease involving the heart, kidney, or liver, in particular: a.) New York Heart Association classification stage II, III, or IV congestive heart failure; b.) Coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infraction) within 3 months of first dose of study drug; c.) Any other primary cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
- •Had any other severe concurrent disease, or had a history of serious organ dysfunction or disease involving the heart had any prior treatment with Clofarabine.
- •Had a diagnosis of another malignancy, unless the participants had been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions: a.) Participants with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease -free duration, were eligible for this study if definitive treatment for the condition had been completed. b.) Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen values were also eligible for this study if hormonal therapy had been initiated or a radical prostatectomy had been performed.
- •Had prior positive test for the Human Immunodeficiency Virus.
- •Had currently active gastrointestinal disease, or prior surgery that might affect the ability of the participants to absorb oral Clofarabine.
- •Participating in other concurrent investigational protocols that were not restricted to data and/or sample collection for participants demographic and/or sample collection for participants demographic and/or disease purposes.
- •Had prior treatment with a known nephrotoxic drug within 2 weeks of the first dose of study drug, unless the participants had a calculated GFR >30 at 2 time points no <7 days apart during the 2-week period prior to the first dose of study drug.
研究组 & 干预措施
Clofarabine 55 mg/day
Experimental
Participants received Clofarabine 55 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
干预措施: Clofarabine (Drug)
Clofarabine 35 mg/day
Experimental
Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
干预措施: Clofarabine (Drug)
Clofarabine 25 mg/day
Experimental
Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
干预措施: Clofarabine (Drug)
结局指标
主要结局
Percentage of Participants With Overall Response
时间窗: From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)
Overall Response: complete remission(CR) or marrow CR or partial remission (PR), or hematologic improvement (HI) in participants with myelodysplastic syndromes (MDS);CR or CR with incomplete count recovery(CRi),or PR in participants with secondary acute myeloid leukemia (sAML). Per International Working Group (IWG) criteria, CR:\<= 5% myeloblasts in bone marrow; persistent dysplasia had to be noted; peripheral blood showing hemoglobin (Hgb)\>=11g/dL, platelets \>=100\*10\^9/L,neutrophils \>=1\*10\^9/L, blasts 0%. Marrow CR:\<=5%myeloblasts in bone marrow and decreased by \>=50% over pretreatment; any HI response in peripheral blood. CRi: meeting all criteria for CR except for residual thrombocytopenia (platelet \<100\*10\^9/L) or neutropenia (ANC \<1.0\*10\^9/L). PR: all CR criteria if abnormal before treatment except that marrow blasts should have decreased by \>=50% over pretreatment but still \>5%. HI: meeting any of the erythroid, platelet, or neutrophil improvement categories for at least 8 weeks.
次要结局
- Number of Participants Who Achieved Hematologic Improvement (HI)(From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years))
- Percentage of Participants Achieving Overall Remission (OR)(From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years))
- Time to Acute Myeloid Leukemia (AML) Transformation(From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years))
- Duration of Response (DoR)(From first documentation of response to date of documentation of disease relapse, progression or death due to any cause, whichever occurs first (maximum study duration: up to 4 years))
- Overall Survival (OS)(From date of first dose of study drug until date of death due to any cause (maximum study duration: up to 4 years))
- Number of Participants Who Reported Death Within 30 Days of First Dose(Within 30 days of first dose administered on Day 1 of Cycle 1)
- PK Parameter: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Plasma Concentration (AUC0-last) of Clofarabine(Pre-dose and at 1, 3, and 5 hours Post-dose on Day 1 of Cycle 1)
- Maximum Tolerated Dose (MTD) of Oral Clofarabine(Cycle 1 (28 days))
- Number of Participants With Unacceptable Drug-related Toxicities During Cycle 1(Cycle 1 (28 days))
- Number of Participants With Febrile Neutropenia(From Baseline up to 45 days post last dose of study drug (maximum study duration: up to 4 years))
- Pharmacokinetics (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Clofarabine(Pre-dose and at 1, 3, and 5 hours Post-dose on Day 1 of Cycle 1)
- PK Parameter: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Clofarabine(Pre-dose and at 1, 3, and 5 hours Post-dose on Day 1 of Cycle 1)
- Number of Participants With Adverse Events (AEs)(From Baseline up to 45 days post last dose of study drug (maximum duration: up to 4 years))
研究者
研究点 (6)
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