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Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

2016年11月7日 更新者:Fabio Pires de Souza Santos、Hospital Israelita Albert Einstein

Evaluation of the Incidence and Prognostic Impact of Molecular and Genetic Abnormalities in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myeloproliferative Neoplasms

The objective of this study is to describe the prevalence and prognostic impact of the most common genetic abnormalities in patients with Myeloid Neoplasms, including Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPN), Myelodysplastic Syndromes (MDS) and Myeloproliferative/Myelodysplastic Neoplasms. Patients will have samples of blood and/or bone marrow collected and sent to Hospital Israelita Albert Einstein for analysis and storage.

Patients with a diagnosis of Acute Myeloid Leukemia will be treated according to an uniform protocol.

研究概览

研究类型

介入性

注册 (实际的)

455

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • SP
      • Sao Paulo、SP、巴西、05651901
        • Hospital israelita Albert Einstein

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Acute Myeloid Leukemia-Intensive Chemotherapy

Inclusion Criteria:

  • Diagnosis of AML according to WHO criteria
  • Age greater than 18 years
  • Performance status (ECOG) between 0-2
  • Adequate liver and kidney function
  • Signed Informed Consent form
  • No prior therapy for AML, except use of hydroxyurea for control of elevated white blood cell counts
  • Adequate contraception for fertile men and women
  • Eligible for intensive chemotherapy (as judged by the treating physician)

Exclusion Criteria:

  • Acute myeloid leukemia with retinoic acid receptor alpha (RARA) translocations (APL, acute promyelocytic leukemia)
  • Pregnant women
  • HIV-positivity
  • New York Heart Association class III and IV congestive heart failure
  • Patient refuses to use adequate contraception
  • History of hypersensibility to any of the used chemotherapy drugs
  • Patient refuses to sign informed consent form

Acute Myeloid Leukemia-Non-Intensive Chemotherapy

Inclusion Criteria:

  • Diagnosis of AML according to WHO criteria
  • Age greater than 18 years
  • Signed Informed Consent form
  • No prior therapy for AML, except use of hydroxyurea for control of elevated white blood cell counts
  • Adequate contraception for fertile men and women
  • Non-eligible for intensive chemotherapy (as judged by the treating physician)

Exclusion Criteria:

  • Acute myeloid leukemia with RARA translocations (APL, acute promyelocytic leukemia)
  • Pregnant women
  • HIV-positivity
  • Patient refuses to use adequate contraception
  • History of hypersensibility to any of the used chemotherapy drugs
  • Patient refuses to sign informed consent form

Chronic Myeloid Disorders:

Inclusion Criteria:

  • Diagnosis of Myeloproliferative Neoplasm or Myelodysplastic Syndrome or Myeloproliferative/Myelodysplastic Neoplasm according to WHO criteria
  • Age greater than 18 years
  • Signed Informed Consent form

Exclusion Criteria:

  • Patient refuses to sign informed consent form

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:基础科学
  • 分配:非随机化
  • 介入模型:并行分配
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
其他:AML-Intensive Chemotherapy

Patients with Acute Myeloid Leukemia fit for intensive chemotherapy Patients will receive Induction Chemotherapy, and CR will be evaluated after 28 days.

Patients who achieve CR post-induction chemotherapy will receive post-remission therapy according to risk:

  • Low risk patients: Consolidation chemotherapy or Autologous stem cell transplantation
  • Intermediate and high-risk patients: Allogeneic stem cell transplantation Patients who do not achieve CR may receive one second induction cycle, and if CR is achieved may proceed to post-remission therapy as per above. Patients who do not achieve CR after two cycles of induction will be deemed refractory and removed from the study.

Induction chemotherapy for patients with AML eligible for intensive chemotherapy:

  • Cytarabine 200 mg/m2 IV continuous infusion days 1-7
  • Daunorubicin 90 mg/m2 intravenous piggyback days 1-3
其他名称:
  • 阿糖胞苷C
  • 蒽环类
  • 7+3
  • 柔红霉素
  • 3+7

Consolidation chemotherapy for patients eligible for intensive chemotherapy with low-risk AML or patients with intermediate-/high-risk AML who do not have matched donors:

-Cytarabine 1.5 g/m2 IV in 3 hours days 1, 3 and 5 for 3 cycles

其他名称:
  • 阿糖胞苷C
  • 阿糖胞苷

Autologous Stem Cell Transplantation for consolidation of patients eligible for intensive chemotherapy with low-risk AML or patients with intermediate-/high-risk AML who do not have matched donors:

  • Busulfan 1 mg/Kg PO q6h or 130 mg/m2 IV once daily days -7 to -4
  • Cyclophosphamide 60 mg/Kg IV once daily days -3 and -2
其他名称:
  • ASCT
  • ABMT
  • Autologous Bone Marrow Transplantation

Allogeneic Stem Cell Transplantation for consolidation of patients eligible for intensive chemotherapy with intermediate-/high-risk AML

Conditioning regimen:

  • Busulfan 1 mg/Kg PO q6h or 130 mg/m2 IV once daily days -7 to -4
  • Cyclophosphamide 60 mg/Kg IV once daily days -3 and -2 or Fludarabine 40 mg/m2 IV once daily days -7 to -4
其他名称:
  • 同种异体干细胞移植
  • 同种异体骨髓移植
其他:AML-Non-intensive chemotherapy

Patients with acute myeloid leukemia not fit for intensive chemotherapy Patients will receive induction chemotherapy with either low dose cytarabine or decitabine. Assignment to each drug will depend on drug availability and physician discretion. No randomization will be done between the drugs.

Cycles will be repeated every 28 days. Patients who achieve CR will continue to post-consolidation therapy with either cytarabine or decitabine, based on the induction therapy received. Patients will receive a maximum of 4 cycles until achieving CR, if no response is seen after 4 cycles patients will be deemed refractory.

Chemotherapy for patients with AML who are not fit for intensive chemotherapy:

  • Cytarabine 60 mg/m2 subcutaneous (SQ) bid days 1-5 (until CR or maximum 4 cycles)
  • Cytarabine 40 mg/m2 SQ bid days 1-5 (after CR, until a maximum of 3 years of therapy or relapse, whichever comes first)
其他名称:
  • Low dose ara-C
  • LDAC

Chemotherapy for patients with AML who are not fit for intensive chemotherapy:

  • Decitabine 20 mg/m2 IV once daily days 1-10 (until CR or maximum 4 cycles)
  • Decitabine 20 mg/m2 IV once daily days 1-5 (after CR, until a maximum of 3 years of therapy or relapse, whichever comes first)
其他名称:
  • 达科根
  • 解码器
  • 2-aza-5´-deoxycytidine
无干预:Chronic Myeloid Disorders

Patients with Chronic Myeloid Disorders:

  • Myeloproliferative Neoplasms
  • Myelodysplastic Syndromes
  • Myeloproliferative/Myelodysplastic Neoplasms

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Prevalence of molecular and cytogenetic abnormalities
大体时间:2 years
As assessed by results of molecular and cytogenetic tests and frequency in the population studied
2 years

次要结果测量

结果测量
措施说明
大体时间
Overall survival
大体时间:5 years
Evaluation of 5-years overall survival in patients with Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms
5 years
Response rate
大体时间:1 month
Evaluate complete remission (CR) rate at 1 month for patients with Acute Myeloid Leukemia who received induction chemotherapy. Complete remission was defined by the presence of < 5% blasts in the bone marrow (BM) with > 1 x 10^9/L neutrophils and >100x10^9/L platelets in the peripheral blood (PB)
1 month
Disease Free Survival
大体时间:5 years
Evaluate rate of 5-years disease-free survival in patients with Acute Myeloid Leukemia who enter complete remission after induction chemotherapy
5 years
Cumulative incidence of relapse and non-relapse mortality
大体时间:5 years
Evaluate 5-years cumulative incidence of relapse and non-relapse mortality in patients with Acute Myeloid Leukemia who achieve complete remission following induction chemotherapy
5 years
Number of participants with adverse events as a measure of safety and tolerability
大体时间:1 year
Evaluate hematological and non-hematological toxicity in patients with Acute Myeloid Leukemia treated according to the protocol. Toxicity will be graded as per the National Cancer Institute Common Toxicity Criteria for Adverse Events v4.0.3
1 year
Cumulative Incidence of Transformation to Acute Myeloid Leukemia
大体时间:5 years
Evaluate 5-years incidence of transformation to Acute Myeloid Leukemia in patients with Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms
5 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 研究主任:Fabio P Santos, MD、Hospital israelita Albert Einstein
  • 学习椅:Nelson Hamerschlak, MD, PhD、Hospital israelita Albert Einstein

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2012年10月1日

初级完成 (实际的)

2014年12月1日

研究完成 (实际的)

2016年11月1日

研究注册日期

首次提交

2013年1月2日

首先提交符合 QC 标准的

2014年3月10日

首次发布 (估计)

2014年3月12日

研究记录更新

最后更新发布 (估计)

2016年11月8日

上次提交的符合 QC 标准的更新

2016年11月7日

最后验证

2016年11月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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