Myeloablative T- Replete Haploidentical PBSCT for Patients Without MRD or MUD

针对无 MRD 或 MUD 的患者进行清髓 T 填充单倍相合 PBSCT

• 批准号: 8485657
• 负责人: Asad Bashey
• 金额: $ 10.35万
• 依托单位: NORTHSIDE HOSPITAL ATLANTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-22 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8485657
• 关键词: Acute Graft Versus Host Disease; Address; Adult; Adverse event; Allogenic; Blood; CD3 Antigens; Caring; Cell Transplants; Cells; Chimerism; Cost Analysis; Cyclophosphamide; Disease-Free Survival; Engraftment; Ethnic group; Graft Rejection; Healthcare; Hematologic Neoplasms; Hematopoietic; Immune; Incidence; Infection; Instruction; Life; Malignant Neoplasms; Marrow; Minority; Myeloid Cells; Myeloproliferative disease; Nature; Outcome; Patients; Peripheral Blood Stem Cell; Peripheral Stem Cell Transplantation; Phase; Phase II Clinical Trials; Pilot Projects; Protocols documentation; Public Health; Race; Randomized; Regimen; Relapse; Research; Safety; Siblings; Source; Stem cell transplant; T-Cell Depletion; T-Lymphocyte; Testing; Therapeutic; Toxic effect; Transplantation; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; Underrepresented Minority; chronic graft versus host disease; comparative; conditioning; cost; effective therapy; ethnic minority population; graft vs host disease; hematopoietic cell transplantation; high risk; in vivo; mortality; novel strategies; peripheral blood; pilot trial; reconstitution

DESCRIPTION (provided by applicant): Many patients, particularly those from ethnic minorities, are unable to access the therapeutic benefit of allogeneic hematopoietic cell transplantation due to the lack of a suitable donor. For such patients, umbilical cord blood can offer an alternative source of hematopoietic cells. However, adults typically require the concurrent use of two cord blood units (DCBT) at considerable expense. In adults such transplants are also associated with delayed immune reconstitution, increased rate of infections and a higher treatment related mortality than transplants from conventional donors. Recently the use of haploidentical (partially matched related donor) hematopoietic cell transplants (haplo-HCT) using T-cell-replete marrow grafts and post- transplant cyclophosphamide (PTCy), have been shown to produce high rates of engraftment and low treatment related mortality (TRM) when used with a non-myeloablative preparative regimen, in patients who lack conventional donors. However, such transplants have limited efficacy in aggressive/advanced myeloid malignancies because of a high relapse rate. In an institutional pilot trial, we have assessed the use of T- replete mobilized peripheral blood (PBSC) and a myeloablative preparative regimen with haplo-HCT + PTCy. Despite the advanced and high-risk nature of the malignancies treated, estimated 6 month TRM was 14% and disease-free survival was 72%. All patients engrafted and developed full donor chimerism in CD3+ and CD33+ cells by day +30. A multi-institutional phase II trial is therefore proposed within the BMT CTN to confirm these encouraging results. The proposed trial will test the hypothesis that this novel approach to myeloablative haplo-HCT is safe and effective when used in a multi-institutional setting. Upon successful completion of this phase II trial, a randomized phase 111 comparison is proposed between this approach to haplo-HCT and myeloablative DCBT. The objective of this phase 111 study will be to directly compare these two approaches to alternative donor transplantation with respect to safety, toxicity, efficacy, cost and immune reconstitution. This trial would definitively determine the best option for myeloablative transplantation in patients with advanced malionancies who lack a matched-sibling or matched unrelated donor RELEVANCE (See instructions): The proposed research addresses a significant current deficiency in public health. Specifically, it tests a novel strategy that will enable curative myeloablative blood stem cell transplants in patients (particularly those from underserved minorities) who are currently unable to access them due to lack of a conventional donor. If successful, it will transform the standard-of-care by offering life-saving therapy to patients who would have died from their cancer and close a major disparity in healthcare access for ethnic minorities.

描述（由申请人提供）：由于缺乏合适的供体，许多患者，特别是来自少数民族的患者无法获得同种异体造血细胞移植的治疗益处。对于这类患者，脐带血可以提供另一种造血细胞来源。然而，成人通常需要同时使用两个脐带血单位（DCBT），费用相当高。在成人中，这种移植也与免疫重建延迟、感染率增加和治疗相关死亡率高于传统供体移植有关。最近，在缺乏传统供体的患者中，使用t细胞骨髓移植和移植后环磷酰胺（PTCy）进行单倍体相同（部分匹配的相关供体）造血细胞移植（haploo - hct），当与非清髓准备方案一起使用时，已被证明可以产生高的移植率和低的治疗相关死亡率（TRM）。然而，由于高复发率，这种移植对侵袭性/晚期髓系恶性肿瘤的疗效有限。在一项机构试点试验中，我们评估了T-充满动员外周血（PBSC）和单倍hct + PTCy的清髓准备方案的使用。尽管所治疗的恶性肿瘤是晚期和高风险的，但估计6个月的TRM为14%，无病生存率为72%。所有患者在第30天移植并形成CD3+和CD33+细胞的完全供体嵌合。因此，建议在BMT CTN内进行多机构II期试验，以确认这些令人鼓舞的结果。拟议的试验将验证这种新的清髓单倍hct方法在多机构环境下安全有效的假设。在II期试验成功完成后，建议将该方法与单倍hct和清髓性DCBT进行随机111期比较。这项111期研究的目的是直接比较这两种方法与替代供体移植在安全性、毒性、有效性、成本和免疫重建方面的差异。该试验将明确确定晚期恶性肿瘤患者清除骨髓移植的最佳选择，这些患者缺乏匹配的兄弟姐妹或匹配的非亲属供体相关性（见说明）：拟议的研究解决了当前公共卫生的一个重大缺陷。具体来说，它测试了一种新的策略，该策略将使由于缺乏传统供体而目前无法获得治疗的患者（特别是那些来自服务不足的少数民族的患者）能够进行清骨髓造血干细胞移植。如果成功，它将通过为可能死于癌症的患者提供挽救生命的治疗来改变护理标准，并缩小少数民族在获得医疗保健方面的巨大差距。