Dose Escalation Study of Clofarabine in Combination With Cytarabine (Ara-C) and G-CSF Priming for Relapsed or Refractory Acute Myeloid Leukemia (AML) Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Response Rates by Salvage Number
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 stopping them from dividing. Colony stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy.
PURPOSE: This phase I trial is studying the side effects and best dose of clofarabine to see how well it works when given together with cytarabine and G-CSF in treating patients with relapsed or refractory acute myeloid leukemia
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of clofarabine, and the dose-limiting toxicities of the combination of clofarabine and cytarabine with G-CSF priming, in the treatment of patients with relapsed or refractory AML.
SECONDARY OBJECTIVES:
I. To determine the hematological and non-hematological side effect profile of the combination of clofarabine, cytarabine, and G-CSF.
II. To determine the efficacy of clofarabine in combination with cytarabine and G-CSF priming in the treatment of patients with relapsed or refractory AML.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG performance status 0-2
- •Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent
- •Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
- •Male and female patients must be willing to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
- •Serum Total or Direct bilirubin =< 1.5 times upper limit of normal (ULN)
- •Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 times ULN
- •Diagnosis of acute myeloid leukemia by WHO criteria, either relapsed or refractory; acute promyelocytic leukemia [acute promyelocytic leukemia with t(15;17)(q22;q12) and variants] would be eligible only after failure of a regimen containing arsenic trioxide
- •Serum creatinine =< 1.0 mg/dL; if serum creatinine > 1.0 mg/dl, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m^2
- •Alkaline phosphatase =< 2.5 times ULN
排除标准
- •Use of investigational agents within 30 days or initiation of any other anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea, and intrathecal therapy for leukemic meningitis
- •Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
- •Pregnant or lactating patients
- •Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
- •Have any other severe concurrent disease, history of serious organ dysfunction, or disease involving the heart, kidney, liver (including symptomatic hepatitis, veno-occlusive disease, or hepatic graft-versus-host disease [for acute >= grade 2]), or other organ system dysfunction
- •No concomitant cytotoxic therapy or investigational therapy is allowed during the study with the exception of intrathecal therapy for leukemic meningitis; intrathecal therapy must not be given during or within 24 hours of any 5 day Clofarabine/Cytarabine treatment period
- •To the extent possible, use of nephrotoxic (e.g., vancomycin, amphotericin B, etc) and hepatotoxic (e.g., voriconazole, cyclosporine, etc) agents is to be avoided during clofarabine; use of alternative medications (e.g., herbal or botanical for anticancer purposes) is not permitted during the entire study period
- •Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol
- •More than two failed induction attempts for initial diagnosis or current relapse; for patients enrolled under part III of the protocol, patients must be at first salvage after relapse less than one year from complete remission, or salvage after initial induction chemotherapy
- •Allogeneic transplant recipients on immunosuppression or on treatment for GVHD
研究组 & 干预措施
Arm I
See Detailed Description
干预措施: clofarabine (Drug)
Arm I
See Detailed Description
干预措施: cytarabine (Drug)
Arm I
See Detailed Description
干预措施: filgrastim (Biological)
结局指标
主要结局
Response Rates by Salvage Number
时间窗: 45 days after the last dose of clofarabine
Number of participants in each Salvage number category who achieved a Complete Remission. Salvage number refers to whether treatment with GCLAC on this study was the pariticipant's first salvage regimen (1), second salvage regimen (2), or third or greater salvage regimen (3 or greater).
Maximum Tolerated Dose of Clofarabine
时间窗: 45 days after the last dose of clofarabine
Dose-limiting Toxicity as Assessed by NCI CTCAE v3.0
时间窗: 45 days after the last dose of clofarabine
Response Rates by Cytogenetic Risk Category
时间窗: 45 days after the last dose of clofarabine
Number of participants who achieved Complete Remission (less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) under each cytogenetic risk category.
Response Rates by Cytogenetic Risk Category and Clofarabine Dose
时间窗: 45 days after the last dose of clofarabine
Number of participants under each Cytogenetic Risk Category and Clofarabine dose who achieve CR (Complete Remission = less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) or CRp (Complete Remission, but with a platelet count of less than 100,000/microL).
Response Rates by Duration First Complete Remission (CR1)
时间窗: 45 days after the last dose of clofarabine
Number of participants whose first Complete Remission lasted 0, 1-6, 6-12, or greater than 12 months. Only those participant who had a first CR are included in this data.
次要结局
- Hematologic and Non-hematologic Side Effect Profile(45 days after the last dose of clofarabine)
- Efficacy(At five years after the last dose of clofarabine)
- Disease-free Survival(At five years after the last dose of clofarabine)
- Overall Survival(At five years after the last dose of clofarabine)
研究者
Pamela S Becker
Principal Investigator
University of Washington