NK Cells Infusion as Consolidation Treatment of Acute Myeloid Leukemia in Children and Adolescents
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 6
- 主要终点
- Relapse-free rate after allogeneic haploidentical NK cell infusion
研究概览
简要总结
The main goal of this study is to evaluate the anti-relapse prophylactic activity of inoculating Natural Killer (NK) cells as consolidation therapy of acute myeloid leukemia in paediatric patients with cytologic remission. The patients included have intermediate risk of relapse and no indication for allogeneic hematopoietic stem cell transplantation.
After the standard induction and consolidation chemotherapy treatment, patients will receive five days of fludarabine to try to kill any minimal residual disease and prevent NK cell rejection. Two different NK cells infusions will be performed within one week (day 0 and 7). Interleukin 2 (IL-2) will be administrated to increase the cytotoxic activity of NK cells.
详细描述
Hypothesis:
NK cells are the natural defence against cancer cells. Thus, supplementing compatible NK cells from a related donor might increase the probability to eliminate any residual chemotherapy resistant cell in Acute myelogenous leukemia patients.
Description:
NK cells will be donated from a compatible family member who has a certain genetic code in their blood, called HLA, which partly matches patient genetic code, reducing any potential rejection. Interleukin-2 is co administrated during NK cell treatment to improve effectiveness.
Methodology:
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 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged between 0 and 21 years, diagnosed with AML in first cytological remission who have completed the induction and consolidation chemotherapy phases and no criteria for allogeneic hematopoietic stem cell transplantation (HSCT), ie patients who have responded well to induction lacking donor HLA identical relative and do not have high-risk cytogenetic abnormalities.
- •Karnofsky or Lansky Performance Scale (PS) > 60%
- •Mild-moderate (<4) organ functional impairment (liver, kidney, respiratory) according to the criteria of the National Cancer Institute (NCI CTCAE v4).
- •Left ventricular ejection fraction> 39%
- •Adult subjects who have voluntarily signed informed consent before the first study intervention.
- •Minor subjects whose representative / legal guardian has voluntarily signed informed consent before the first study intervention.
- •For mature minors (12 to 17 years old), in addition to the consent signed by the legal guardian, the assent of the child will be obtained.
- •Women of childbearing potential must have a negative pregnancy test at the time inclusion and must agree to use highly effective contraceptive methods (diaphragms plus spermicide or male condom plus spermicide, combined oral contraceptive with a second method of contraceptive implant, injectable contraceptive, permanent intrauterine device, sexual abstinence or partner with vasectomy) while participating in the study and 30 days after the last visit.
- •Presence of a haploidentical donor
排除标准
- •Patients with a history of poor treatment compliance
- •Patients who after a psycho-social assessment are censored as unfit for procedure:
- •Socio-familiar situation that precludes proper participation in the study.
- •Patients with emotional or psychological problems secondary to the illness such as PTSD, phobias, delusions, psychosis, requiring assistance by specialists.
- •Evaluation of the involvement of the family in the patient's health.
- •Inability to understand the information about the trial.
- •Severe (4) organ functional impairment (liver, kidney, respiratory) according to the criteria of the National Cancer Institute (NCI CTCAE v4).
- •They should be considered contraindications, interactions, precautions for use and dose reductions indicated in the respective data sheets.
- •Subjects who have been administered other investigational drugs within 90 days prior to inclusion
研究组 & 干预措施
Natural Killer (NK) Cells + Chemotherapy
Starting on day -6, 60mg/Kg cyclophosphamide by vein will be administrated. Day -5 to -1 fludarabine administrated by vein at 25 mg/m2. 24-48 hours after chemotherapy completion, NK cell infusion will be injected (day 0). On day 7 a second NK cell infusion will be administrated. First infusion consist of 5x10^7/kg NK CD3-CD56+ NK cells. The second NK cell infusion will include up to 5x10^8 CD3-CD56+ cells if no treatment related toxicity occurred. Subcutaneous IL-2 (1x10^6 UI/m2) three times a week for two weeks will be administrated after first NK infusion.
干预措施: cyclophosphamide (Drug)
Natural Killer (NK) Cells + Chemotherapy
Starting on day -6, 60mg/Kg cyclophosphamide by vein will be administrated. Day -5 to -1 fludarabine administrated by vein at 25 mg/m2. 24-48 hours after chemotherapy completion, NK cell infusion will be injected (day 0). On day 7 a second NK cell infusion will be administrated. First infusion consist of 5x10^7/kg NK CD3-CD56+ NK cells. The second NK cell infusion will include up to 5x10^8 CD3-CD56+ cells if no treatment related toxicity occurred. Subcutaneous IL-2 (1x10^6 UI/m2) three times a week for two weeks will be administrated after first NK infusion.
干预措施: Fludarabine (Drug)
Natural Killer (NK) Cells + Chemotherapy
Starting on day -6, 60mg/Kg cyclophosphamide by vein will be administrated. Day -5 to -1 fludarabine administrated by vein at 25 mg/m2. 24-48 hours after chemotherapy completion, NK cell infusion will be injected (day 0). On day 7 a second NK cell infusion will be administrated. First infusion consist of 5x10^7/kg NK CD3-CD56+ NK cells. The second NK cell infusion will include up to 5x10^8 CD3-CD56+ cells if no treatment related toxicity occurred. Subcutaneous IL-2 (1x10^6 UI/m2) three times a week for two weeks will be administrated after first NK infusion.
干预措施: NK cell infusion (Procedure)
Natural Killer (NK) Cells + Chemotherapy
Starting on day -6, 60mg/Kg cyclophosphamide by vein will be administrated. Day -5 to -1 fludarabine administrated by vein at 25 mg/m2. 24-48 hours after chemotherapy completion, NK cell infusion will be injected (day 0). On day 7 a second NK cell infusion will be administrated. First infusion consist of 5x10^7/kg NK CD3-CD56+ NK cells. The second NK cell infusion will include up to 5x10^8 CD3-CD56+ cells if no treatment related toxicity occurred. Subcutaneous IL-2 (1x10^6 UI/m2) three times a week for two weeks will be administrated after first NK infusion.
干预措施: IL-2 (Drug)
结局指标
主要结局
Relapse-free rate after allogeneic haploidentical NK cell infusion
时间窗: Relapse-free rate at three years
Relapse-free rate according to the clinical guidelines. A bone narrow aspirate one month after NK cell infusion and at least once a year during the three-year follow-up will be evaluated for cytomorphological criteria and minimal residue disease (cytometry or real time PCR). Relapse defined as myeloid blast bone marrow presence with the same diagnosis markers, new ones or mixed. From cytologic analysis 25% of blast or minimal residue disease by cytometry (0,01%) and/or molecular level (0,0001%) present at diagnosis with or without cytogenetic alterations.
次要结局
- Adverse events of special interest: administration issues, infections, immunological/allergic/toxic reactions and concomitant drug interactions.(three years)
- Evaluation of donor phenotype by SS-PCR(Three years)
- Evaluation of patient HLA phenotype by SS-PCR(Three years)
- Evaluation of donor KIR haplotype by PCR(Three years)
- Analysis of Hematopoietic chimerism after NK infusion by PCR or flow cytometry(Three years)
- Ligand expression of the activatory (MICA, MICB and ULBPs) or inhibitory (HLA-1) receptors of the NK cells(Three years)
- NK cytotoxic activity(Three years)