A PILOT STUDY OF YTTRIUM-90-LABELED ANTI-CD20 MONOCLONAL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的目的是评估放射性物质抗体（IDEC-Y2B8）与高剂量化疗（BCNU、依托泊苷、Ara-C和Melphalan，或BEAM）联合治疗方案的安全性和有效性，然后进行自体干细胞移植（ASCT）；在诊断为非霍奇金淋巴瘤的患者中，评估该方案的短期和长期并发症。非霍奇金淋巴瘤是一种B淋巴细胞的恶性肿瘤，B淋巴细胞是一种白细胞，通常会产生抗体，帮助抵抗感染。虽然常规化疗和/或放射治疗可以缓解（通过标准临床试验没有疾病的证据），但缓解的时间通常很短，而且会出现复发（疾病复发）。复发性淋巴瘤患者的前景很差。最近的研究表明，高剂量化疗后自体干细胞移植（ASCT）可以使复发性淋巴瘤患者获得长期缓解。BEAM是制备ASCT最常用的高剂量方案之一。ASCT包括在治疗前收集受试者的干细胞（可以成为血细胞的未成熟细胞），并在治疗结束后将这些细胞（通过静脉）送回受试者。然而，这种治疗方案也会出现复发。抗体Rituximab （Rituxan或IDEC-C2B8）已被证明在大约一半接受治疗的b细胞淋巴瘤患者中产生缓解。在先前的研究中，该抗体已被证明可以选择性地定位和破坏b细胞，包括b细胞淋巴瘤，并使耐药淋巴瘤细胞对化疗变得敏感。在IDEC-Y2B8中加入一种名为钇的放射性物质（创造一种名为IDEC-Y2B8的放射性组合），可以将辐射直接携带到肿瘤部位，从而增强抗肿瘤效果。在过去对IDEC-Y2B8的研究中，大约三分之二的b细胞淋巴瘤患者在治疗后肿瘤缩小超过50%，其中四分之一的患者肿瘤完全消失。反应持续时间约为12个月。本研究将使用强化、高剂量化疗（BEAM）和IDEC-Y2B8，然后进行ASCT。本研究将试图确定这种联合治疗方案的安全性和有效性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purposes of this study are to 1> evaluate the safety and effectiveness of a treatment regimen using an antibody attached to a radioactive substance (IDEC-Y2B8) in combination with high-dose chemotherapy (with the drugs BCNU, Etoposide, Ara-C and Melphalan, or BEAM) followed by autologous stem cell transplant (ASCT); and 2> to evaluate the short-term and long-term complications of this regimen in patients diagnosed with non-Hodgkin's lymphoma. Non-Hodgkin's lymphoma is a malignancy of B lymphocytes, which are the white blood cells that normally make antibodies that help fight infections. Although remission (no evidence of disease by standard clinical tests) can occur with conventional chemotherapy and/or radiation therapy, the length of remission is usually short and relapses (return of disease) occur. The outlook for patients with relapsed lymphoma is poor. Recent studies have shown that intensive, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), can produce long-term remission in patients with relapsed lymphoma. BEAM is one of the most commonly used high-dose regimens for preparation of ASCT. ASCT involves collection of the subject's stem cells (immature cells that can become blood cells) before therapy and return of these cells to the subject (through a vein) after therapy is over. However, relapses also occur with this treatment regimen. The antibody, Rituximab (Rituxan or IDEC-C2B8) has been shown to produce remission in about half of the B-cell lymphoma subjects treated. In previous studies, this antibody has been shown to selectively locate and destroy B-cells, including B-cell lymphoma, and to cause drug-resistant lymphoma cells to become sensitive to chemotherapy. Adding a radioactive substance called Yttrium to IDEC-Y2B8, (creating a radioactive combination called IDEC-Y2B8) allows radiation to be carried directly to tumor sites which can increase the anti-tumor effect. In a past study of IDEC-Y2B8, about two-thirds of the subjects with B-cell lymphoma had shown greater than 50% shrinkage of the tumor after treatment and in one-fourth of them all the tumor was gone. The duration of response was about 12 months. The present study will use intensive, high-dose chemotherapy (BEAM) and IDEC-Y2B8, followed by ASCT. This study will try to determine the safety and effectiveness of this combination regimen.