Clinical Trials in AML

AML 临床试验

• 批准号: 7270267
• 负责人: ELIHU ESTEY
• 金额: $ 25.68万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270267
• 关键词: AMD3100; Accounting; Affect; Antisense Oligonucleotides; Ara-C; BIRC4 gene; Binding; Biological Markers; Blast Cell; CXCR4 gene; Clinical; Clinical Trials; Count; Cytotoxic Chemotherapy; Cytotoxic agent; Data; Disease remission; Doctor of Medicine; Family member; Idarubicin; Life; Marrow; New Agents; Outcome; Patients; Peripheral; Pharmaceutical Preparations; Phosphotransferases; Randomized; Rate; Relapse; Relative (related person); Salvage Therapy; Stem cell transplant; Testing; Time; Validation; Variant; chemotherapy; cytotoxic; inhibitor/antagonist; programs; response

If stem cell transplant is not feasible, M.D. Anderson patients with relapsed AML typically receive investigational agents as first "salvage therapy," particularly if their initial remission has lasted less than one year. Although new agents are available, we do not know how a patient's AML will respond. In this program project, we will study therapies for which a "target" has been proposed, enabling us to examine relationships between clinical response and the status of the putative target (Specific Aim 1). Patients will be randomized, and we will assess their responses as being predictive of the target as well as study the use of biologic markers to assign patients to specific therapies. A confounding difficulty with Specific Aim 1 is the rarity of CR in relapsed AML. This rarity has motivated new definitions of response (e.g. CR p), which are less demanding than the criteria for CR. Preliminary data in untreated patients suggest that, while CR is essential for cure, patients who achieve CR p live longer than patients who achieve neither CR nor CR p after accounting for the time needed to achieve these responses. These data, and the low rate of CR p in the patients to be studied here, have prompted a plan to continue initial therapy in patients as long as they have neither clinical complications nor a rising peripheral blast count. This approach will allow us to compare the effect of various prospectively-defined responses on survival (Specific Aim 2). Two of the agents we will investigate (GX15-070MS, an inhibitor of the BH3 binding domain of Bcl-2 family members, and the kinase inhibitior BAY43-9006) will be given without chemotherapy; we will refer to these as "non-cytotoxic" therapies. The other two agents [the XIAP antisense oligonucleotide AEG35156 and AMD3100, an inhibitor of CXCR4 and thus of the blast cell-marrow stroma interaction), while themselves also non-cytotoxic, will be combined with idarubicin + ara-C (IA); these combinations will thus be called "cytotoxic." We will compare survival in: (a) patients given one of the two cytotoxic combinations only after an unsuccessful trial of one of the two non- cytotoxic agents, (b) patients in whom the alternate approachwas used and (c) patients given IA alone in previous studies. This approach will allow us to test the hypothesis that it appropriate to give some patients with relapsed AML non-cytotoxic therapy as initial treatment for relapse (Specific Aim 3). While such practice is increasingly widespread both in relapsed and untreated AML, its effect on survival remains unknown. Demonstration that, in at least one case, the obvious appeal of this strategy is not offset by a decrease in survival time would presumably be reassuring to patients.

如果干细胞移植不可行，医学博士。患有复发性AML的安德森患者通常接受 研究药物作为第一个“挽救治疗”，特别是如果他们的初始缓解持续时间不到一个月， 年虽然有新的药物可用，但我们不知道患者的AML将如何反应。在这个程序中 项目，我们将研究已提出“目标”的疗法，使我们能够检查关系， 临床反应与推定目标状态之间的关系（具体目标1）。患者将被随机分组， 我们将评估他们的反应，作为预测目标，以及研究生物制剂的使用， 为患者分配特定治疗的标记。具体目标1的一个混淆困难是 复发性AML的CR。这种罕见性促使人们对反应（例如CR p）进行新的定义， 比CR的标准更苛刻。未经治疗的患者的初步数据表明，虽然CR是必不可少的， 对于治愈，达到CR p的患者比在治疗后既没有达到CR也没有达到CR p的患者活得更长。 考虑到实现这些响应所需的时间。这些数据，以及低CR率p在 患者在这里进行研究，促使一项计划，继续对患者进行初始治疗，只要他们有 既没有临床并发症也没有外周血原始细胞计数上升。这种方法将使我们能够比较 各种前瞻性定义的缓解对生存期的影响（具体目标2）。我们将派出两名探员 研究（GX 15 - 070 MS，Bcl-2家族成员的BH 3结合结构域的抑制剂，和激酶 抑制剂BAY 43 -9006）将在没有化疗的情况下给予;我们将这些称为“非细胞毒性” 治疗另外两种药物[XIAP反义寡核苷酸AEG 35156和抑制剂AMD 3100 CXCR 4和因此的母细胞-骨髓基质相互作用），虽然本身也无细胞毒性， 与艾达鲁肽+ ara-C（IA）组合;这些组合因此被称为“细胞毒性的”。“我们将比较 存活率：（a）仅在以下之一的试验失败后给予两种细胞毒性组合之一的患者 两种非细胞毒性药物，（B）使用替代方法的患者和（c）给予 在既往研究中单独使用IA。这种方法将使我们能够测试假设，它适当地给予 一些复发AML患者接受非细胞毒性治疗作为复发的初始治疗（具体目标3）。 虽然这种做法在复发和未经治疗的AML中越来越普遍，但其对生存的影响 仍然未知。证明至少在一个案例中，这一战略的明显吸引力没有被抵消 生存时间的缩短可能会让患者放心。