G-CSF and Plerixafor With Busulfan and Fludarabine for Allogeneic Stem Cell Transplantation for Myeloid Leukemias
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Number of Participants With Grade 4 Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) Plerixafor
研究概览
简要总结
The goal of this clinical research study is to learn about the safety of AMD3100 (plerixafor) and G-CSF (filgrastim) in combination with fludarabine, busulfan, and an allogeneic blood stem cell transplant. This treatment will be studied in patients with acute myeloblastic leukemia (AML), myelodysplastic syndromes (MDS), or Chronic myelogenous leukemia (CML).
详细描述
The Study Treatment:
Fludarabine is a chemotherapy drug that is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.
Busulfan is a chemotherapy drug that is designed to bind to DNA, which may cause cancer cells to die. It is commonly used in stem cell transplants.
Plerixafor and filgrastim are designed to cause cancer cells to move from the bone marrow into the blood stream. This may help to make the cancer cells more sensitive to being killed by the chemotherapy.
An "allogeneic" (from a donor) stem cell transplant is designed to help the recipient's body attack the cancer cells that may remain in the body after chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients age >/=18 to </= 65 years.
- •Diagnosis of AML in first or greater remission, first or subsequent relapse, or primary induction failure; MDS with intermediate or high risk International Prognostic Scoring System (IPSS) score having failed to respond or recurred after chemotherapy; in remission or having active disease after treatment; AML arising from MDS; or CML which has failed to respond to imatinib or other tyrosine kinase inhibitor and has had >5% blasts in the blood or bone marrow. Patients receiving second transplants after relapse are considered in the relapse group.
- •White Blood Count (CBC) </= 20 * 10^9/l.
- •Patients should have a histocompatible, related or unrelated volunteer donor available. A histocompatible donor is defined as HLA matched related donor or an unrelated donor matched for HLA- A, B, C, and DR antigens by high-resolution DNA techniques.
- •Zubrod performance status 0 or 1, or Karnofsky performance status 90-100%.
- •Left ventricular ejection fraction >/= 45 %. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
- •No symptomatic pulmonary disease. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) >/= 50 % of expected, corrected for hemoglobin.
- •Serum creatinine </=1.5 mg/dl.
- •Serum glutamic pyruvic transaminase (SGPT) </= 200 IU/ml unless related to the malignancy.
- •Total serum bilirubin </=1.5 mg/dl (unless Gilbert's syndrome) and alkaline phosphatase </=2.5 times laboratory standard upper limit of normal (ULN).
- •Patient or patient's legal representative able to sign informed consent.
排除标准
- •History of HIV positive.
- •Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
- •Pleural/pericardial effusion or ascites estimated >/= 1 liter.
- •Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy.
- •History of acute hepatitis, chronic active hepatitis or cirrhosis.
- •Patients with class 3 or 4 angina (New York Heart Association (NYHA) criteria).
研究组 & 干预措施
Phase II
ATG + MTD Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: ATG (Thymoglobulin) (Drug)
Phase I
ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Plerixafor (Drug)
Phase I
ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Filgrastim (Drug)
Phase I
ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Fludarabine (Drug)
Phase I
ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Busulfan (Drug)
Phase I
ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Allogeneic blood stem cell transplant (Procedure)
Phase I
ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: ATG (Thymoglobulin) (Drug)
Phase II
ATG + MTD Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Plerixafor (Drug)
Phase II
ATG + MTD Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Filgrastim (Drug)
Phase II
ATG + MTD Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Fludarabine (Drug)
Phase II
ATG + MTD Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Busulfan (Drug)
Phase II
ATG + MTD Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant
干预措施: Allogeneic blood stem cell transplant (Procedure)
结局指标
主要结局
Number of Participants With Grade 4 Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) Plerixafor
时间窗: 28 day cycle (Plerixafor Day -7 to Day -4)
Phase I determination of MTD dose of Plerixafor in combination with a fixed dose of Filgrastim where dose limiting toxicity defined as any grade 4 non-hematologic toxicity observed within 28 days from Day 0 (day of transplant).
次要结局
- Number of Participants Alive With no Disease Progression at Time of Allo Transplant(Baseline till transplant, Day -9 to Day 0, to 10 days)
- Engraftment Response Rate: Number of Transplanted Participants With Complete Chimerism at Day 30(30 Days post engraftment)