Phase II Study of Radiolabeled BC8 (Anti-CD45) Antibody Combined With Busulfan and Cyclophosphamide as Treatment for Acute Myelogenous Leukemia in First Remission Followed by HLA-Identical Related Peripheral Blood Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- Disease-free survival (DFS)
研究概览
简要总结
This phase II trial studies how well iodine I 131 monoclonal antibody BC8, busulfan, and cyclophosphamide followed by donor stem cell transplant works in treating patients with acute myeloid leukemia that has decreased or disappeared, but the cancer may still be in the body. Giving chemotherapy drugs, such as busulfan and cyclophosphamide before a donor peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Also, radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the stem cells from a related donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
详细描述
PRIMARY OBJECTIVES:
I. To determine the efficacy (as measured by survival and disease-free survival) and toxicity of a regimen of busulfan 16 mg/kg and cyclophosphamide 120 mg/kg plus 131I-labeled anti-cluster of differentiation (CD) 45 antibody (iodine I 131 monoclonal antibody BC8) (delivering a dose of 5.25 gray [Gy] to the normal organ receiving the highest dose) in patients with acute myeloid leukemia (AML) in first remission receiving human leukocyte antigen (HLA)-identical related peripheral blood stem cell (PBSC) transplants.
OUTLINE:
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 intravenously (IV) on day -13.
CHEMOTHERAPY: Patients receive busulfan orally (PO) every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
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
- 16 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with AML in first remission
- •Creatinine < 2.0 mg/dl
- •Bilirubin < 1.5 mg/dl which is expected to exclude patients at high risk of developing veno-occlusive disease of the liver
- •Aspartate aminotransferase (AST) < 1.5 times the upper limit of normal which is expected to exclude patients at high risk of developing veno-occlusive disease of the liver
- •Patients must have an expected survival of > 60 days and must be free of major infection
- •DONOR: genotypic or phenotypic HLA-matched family members; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and DR beta 1 (DRB1) according to Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Guidelines and to the allele level at DQ beta 1 (DQB1)
排除标准
- •Patients with history of or current leukemic involvement of the central nervous system (CNS)
- •Prior radiation to maximally tolerated levels to any normal organ
- •Inability to understand or give an informed consent
- •Patients who are seropositive for human immunodeficiency virus (HIV)
- •Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation
- •Circulating antibody against mouse immunoglobulin
- •DONOR: unrelated donors and donors mismatched for 1 or more HLA antigens
- •DONOR: donors who for psychologic, physiologic or medical reasons are unable to undergo filgrastim (G-CSF)- mobilized PBSC collection or marrow harvesting
- •DONOR: donors who are seropositive for HIV
研究组 & 干预措施
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: iodine I 131 monoclonal antibody BC8 (Radiation)
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: busulfan (Drug)
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: cyclophosphamide (Drug)
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: allogeneic bone marrow transplantation (Procedure)
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: peripheral blood stem cell transplantation (Procedure)
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: cyclosporine (Drug)
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: methotrexate (Drug)
Treatment (radiolabeled BC8, chemotherapy, PBSCT)
RADIOLABELED ANTIBODY: Patients receive iodine I 131 monoclonal antibody BC8 IV on day -13.
CHEMOTHERAPY: Patients receive busulfan PO every 6 hours on days -7 to -4 and cyclophosphamide IV on days -3 and -2.
TRANSPLANT: Patients undergo allogeneic PBSC or BM transplant on day 0.
GRAFT-VS-HOST DISEASE PREVENTION: Patients receive cyclosporine IV or PO every 12 hours on days -1 to 50 with a taper to day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Disease-free survival (DFS)
时间窗: Up to 6 years
Summarized using appropriate time-to-event methods with estimates of the corresponding confidence intervals provided.
次要结局
- Transplant-related mortality(Up to 6 years)
- Relapse of AML patients(Up to 6 years)
- Overall survival (OS)(Up to 6 years)