Natural Killer (NK) Cells and Nonmyeloablative Stem Cell Transplantation for Chronic Myelogenous Leukemia (CML)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of Participants With Molecular Complete Remission at 3 Month Post Transplant
研究概览
简要总结
The goal of this clinical research study is to learn if giving a kind of immune cell called natural killer (NK) cells after chemotherapy will improve the response to a stem cell transplant in patients with CML. The safety of this treatment will also be studied.
详细描述
NK cells may react against leukemia cells, particularly when they are mismatched for certain HLA tissue type proteins. In the lab, the NK cells are separated from the blood using a machine called a CLINIMACs system. This machine uses certain kinds of cells and antibody-coated magnetic beads to separate the NK cells. The drug aldesleukin (interleukin-2, IL-2) is then added to the NK cells to improve their function. The aldesleukin will be washed out of the cell sample before it is given to you.
The NK cells will be donated from a family member who has a certain genetic type in their blood called HLA that partly matches yours. The stem cells you will receive will come from a separate HLA-identical family member or an unrelated donor.
Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.
Busulfan is designed to bind to DNA, which may cause cancer cells to die.
Study Drug Administration:
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 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who meet the following eligibility criteria are eligible for inclusion in this study. Pediatric team to assess eligibility appropriate for patient age.
- •Age </= 70 years of age.
- •Patients with diagnosis of CML in first chronic phase or accelerated phase with less than 15% blast in the blood and bone marrow at study entry which has failed to respond adequately to imatinib by the consensus criteria of Baccarani et al: a) no hematologic remission at 3 months, b) no cytogenetic response at 6 months, c) no major cytogenetic response at 12 months, d) no complete cytogenetic response or major molecular response at >18 months, or e) loss of a response with increasing cytogenetic or molecular evidence of disease. Or are intolerant to tyrosine kinase inhibitor therapy. Or with second or greater chronic phase (with prior transformation who respond to treatment and have <15% blasts at study entry).
- •Histocompatible stem cell donor: Patients must have an HLA matched related or unrelated donor (HLA A, B, C and DR) willing to donate for allogeneic hematopoietic transplantation.
- •Haploidentical NK cell donor: Patients must have a haploidentical relative with the absence of a KIR-ligand (HLA molecule).
- •Performance status: Zubrod </= 2 or Lansky PS greater or equal to 70%.
- •Cardiac function: left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
- •Pulmonary function: no symptomatic pulmonary disease. forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) >/= 50% of expected, corrected for hemoglobin. For pediatric patients, if unable to perform pulmonary function tests (most children < 7 years of age), pulse oximetry >/= 92% on room air by pulse oximetry.
- •Renal function: Serum creatinine </= 1.8mg/dl or creatinine clearance greater or equal than 40 cc/min. Creatinine for pediatric patients </= 1.5 mg/dl or </= 2 times upper limit of normal for age (whichever is less).
- •Liver function: Bilirubin </= 1.5 mg/dl (unless Gilbert's syndrome), ALT or AST </= 200 IU/ml for adults unless related to underline disease. For pediatric patients conjugated (direct) bilirubin <2x upper limit of normal, ALT or AST <5 times upper limit of normal.No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
- •Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent. Assent as is age appropriate.
排除标准
- •Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The Protocol PI is the final arbiter of eligibility.
- •Pleural/pericardial effusion or ascites estimated to be >1L
- •HIV-positive.
- •Breast feeding or pregnancy. Pregnancy means a 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.
- •Known allergy to mouse proteins
- •Active hepatitis B or C infection.
研究组 & 干预措施
NK Infusion + Chemotherapy
Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.
干预措施: Fludarabine (Drug)
NK Infusion + Chemotherapy
Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.
干预措施: Busulfan (Drug)
NK Infusion + Chemotherapy
Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.
干预措施: Interleukin-2 (Drug)
NK Infusion + Chemotherapy
Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.
干预措施: Anti-Thymocyte Globulin (Drug)
NK Infusion + Chemotherapy
Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.
干预措施: Allogeneic related Stem Cell Transplant (Procedure)
NK Infusion + Chemotherapy
Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.
干预措施: Tacrolimus (Drug)
NK Infusion + Chemotherapy
Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.
干预措施: Methotrexate (Drug)
NK Infusion + Chemotherapy
Fludarabine 40 mg/m2 intravenous (IV) daily for 4 days, immediately followed by Busulfan 130 mg/ m2 IV every 24 hours and NK cell infusion IV.
干预措施: G-CSF (Drug)
结局指标
主要结局
Number of Participants With Molecular Complete Remission at 3 Month Post Transplant
时间窗: Baseline to up to 4 months post-transplant
Molecular Complete Remission is defined as participant alive and engrafted with molecular complete remission 100 days post transplant where molecular complete response is no BCR-ABL transcripts detected and engraftment is defined as the evidence of donor derived cells (more than 95%) by chimerism studies in the presence of neutrophil recovery by day 28 post stem cell infusion.
次要结局
未报告次要终点