Treatment of Acute Myelogenous Leukemia With Busulfan and Etoposide Followed by Autologous or Syngeneic Stem Cell Rescue and Low-Dose Interleukin 2 (IL-2) Immunotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Toxicity Associated With Aldesleukin Treatment After Stem Cell Rescue
研究概览
简要总结
This phase II trial studies the side effects and how well giving busulfan and etoposide followed by peripheral blood stem cell transplant (PBSCT) and low-dose aldesleukin works in treating patients with acute myeloid leukemia (AML). Drugs used in chemotherapy, such as busulfan and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A PBSCT may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more cancer cells are killed. Aldesleukin may stimulate the white blood cells to kill cancer cells. Giving busulfan and etoposide together followed by PBSCT and aldesleukin may be an effective treatment for AML.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the toxicity and overall survival of high dose Bu (busulfan)/VP-16 (etoposide) followed by post-transplant low-dose interleukin (IL)-2 (aldesleukin) in patients with AML.
SECONDARY OBJECTIVES:
I. To estimate the rate of relapse associated with this regimen.
OUTLINE:
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
- — 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient must have AML that falls into one of the following categories:
- •AML in 1st complete remission (CR) with intermediate or high risk of relapse following conventional therapy; at least, one of the following features is needed:
- •Patient required more than one cycle of induction to achieve first CR
- •White blood cell count (WBC) > 100,000/mm^3 at diagnosis
- •Any of the following cytogenetic abnormalities: inv (3), t(3:3), del (5q) or -5, 11q23, del(7q) or -7, del (20q) or -20, abnormal 12p, +11 or t8
- •Any other abnormalities or combination of abnormalities which would predict intermediate or high risk of relapse
- •AML beyond first CR
- •Any patient with an identical twin donor who also meets the criteria above
- •Patients with AML in 1st CR should receive at least two cycles of consolidation chemotherapy prior to mobilization and transplant
- •Patients must have an adequate number of stem cells previously collected (i.e., > 2 x 10^8 total nucleated cell [TNC] of bone marrow [BM]/kg or 4 x 10^6 [CD]34+ PBSC/kg, unless approved otherwise by Dr. Holmberg); prior to stem cell collection patients must be documented to be in remission and to have received two cycles of consolidation therapy after induction therapy
- •Pre-Study tests have been performed
- •Patient must sign an institutional review board (IRB) approved informed consent, conforming with federal and institutional guidelines
排除标准
- •Patients with good risk AML defined by cytogenetic evaluation with these abnormalities: inversion 16 or t8;21
- •Patient's life expectancy is severely limited by diseases other than AML
- •Patient is human immunodeficiency virus (HIV) seropositive
- •Patient is pregnant
- •Patient's creatinine > 2.0 mg/dl
- •Patient's total bilirubin > 2.0 mg/dl (unless Gilbert's disease)
- •Or serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) >= 2.5 x upper limit of normal (ULN) not due to leukemia
- •Patient has a history of congestive heart failure, uncontrolled arrhythmias or left ventricular ejection fraction (LVEF) < 50%
- •Patient has an unrelated human leukocyte antigen (HLA) matched donor and is eligible for a higher priority Fred Hutchinson Cancer Research Center (FHCRC) protocol (for FHCRC patients only)
- •Patient has an HLA matched or one antigen mismatch family donor available
- •Patients with a significant active infection that precludes transplant
- •Patients with a Karnofsky Performance Score less than 70
研究组 & 干预措施
Treatment (chemo, stem cell rescue, interleukin therapy)
PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3.
STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0.
POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks.
干预措施: busulfan (Drug)
Treatment (chemo, stem cell rescue, interleukin therapy)
PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3.
STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0.
POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks.
干预措施: etoposide (Drug)
Treatment (chemo, stem cell rescue, interleukin therapy)
PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3.
STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0.
POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks.
干预措施: aldesleukin (Biological)
Treatment (chemo, stem cell rescue, interleukin therapy)
PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3.
STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0.
POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks.
干预措施: peripheral blood stem cell transplantation (Procedure)
结局指标
主要结局
Toxicity Associated With Aldesleukin Treatment After Stem Cell Rescue
时间窗: IL-2 administration to one month after completion of IL-2 treatment
Toxicity during IL-2 therapy of any of the following per NCI Common Toxicity version 3: grade 2, 3, 4, or 5 CNS (except grade 0-3 malaise, fatigue, anxiety and depression) toxicity; grade 3, 4, or 5 non-CNS or non-hematologic toxicity; any grade 4 or 5 hematologic toxicity.
Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin
时间窗: From date of transplant to date of death from any cause, assessed up to 178 months
Estimated by the method of Kaplan and Meier.
Toxicity Associated With High-dose Busulfan and Etoposide Followed by Stem Cell Rescue
时间窗: Day -7 of transplant to 100 days post transplant
Toxicity is defined as any grade 3 or grade 4 toxicity per the Bearman toxicity grading criteria following Busulfan and Etoposide high-dose chemotherapy, stem cell transplant, and the inability to recover sufficiently by day 100 to start IL-2 therapy.
次要结局
- Proportion of Patients Who Relapsed Associated With the Regimen(From date of transplant to date of death from any cause, assessed up to 178 months)
研究者
Leona Holmberg
Principal Investigator
Fred Hutchinson Cancer Center