Bone Marrow Transplantation With Specially Treated Bone Marrow in Treating Patients With Hematologic Cancer That Have Not Responded to Previous Therapy
A Phase I Open-Label, Safety Study of Haploidentical Bone Marrow Transplantation (BMT) After Ex Vivo Treatment of Bone Marrow With Anti-B7.1 and Anti-B7.2 Antibodies
RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment of the donor bone marrow with the patient's white blood cells and a monoclonal antibody may prevent this from happening.
PURPOSE: Phase I trial to study the effectiveness of bone marrow transplantation with specially treated bone marrow in treating patients who have hematologic cancer that has not responded to previous therapy.
研究概览
地位
详细说明
OBJECTIVES: I. Determine if patients with refractory, high risk hematologic malignancies or bone marrow failure who receive HLA haploidentical bone marrow treated with anti-B7 antibody have normal engraftment. II. Determine if these patients are free of hyperacute graft versus host disease (GVHD), defined as grade D GVHD in the first 10 posttransplant days, when treated with this regimen. III. Determine if these patients have an acceptable incidence of life threatening grade D GHVD in the first 50 posttransplant days following this treatment regimen. IV. Determine the safety and tolerability of this treatment regimen in this patient population.
OUTLINE: This is a multicenter study. Patients undergo leukapheresis to collect white blood cells which are incubated with donor bone marrow cells in the presence of anti-B7.1 and anti-B7.2 antibodies for 36 hours. Patients receive total body irradiation twice daily on days -6 to -3, cyclophosphamide IV daily on days -2 and -1, and methylprednisolone IV every 12 hours for a total of 4 doses on days -2 to 0. Patients are infused with the treated donor bone marrow on day 0. Patients then receive methotrexate IV on days 1, 3, 6, and 11 and leucovorin calcium IV 24 hours after each dose of methotrexate every 6 hours for 3-8 doses each time. Patients also receive cyclosporine IV or orally twice daily on days -2 to 100. Patients are followed every 2 months for 1 year.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
-
-
Massachusetts
-
Boston、Massachusetts、美国、02115
- Dana-Farber Cancer Institute
-
-
Minnesota
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Minneapolis、Minnesota、美国、55455
- University of Minnesota Cancer Center
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-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Age ≤40 years.
Diagnoses-patients with the following hematologic malignancies and bone marrow failure syndromes:
- Acute myelogenous leukemia-induction failure, relapse, second or greater complete remission (CR)
- Acute lymphocytic leukemia-induction failure, relapse, second or greater CR, first CR with t(9;22), t(8;14), or t(4;11)
- Non-Hodgkin's lymphoma (intermediate or high grade) which has failed to achieve CR with at least two induction regimens, relapse, second or greater CR
- Multiple myeloma with poor prognostic features (elevated 0-2 microglobulin or high labeling index)
- Hodgkin's disease in relapse or which fails to achieve CR after two chemotherapy regimens
- Congenital or acquired bone marrow failure - poorly responsive to or intolerant of current therapy
- Myelodysplastic syndrome of all subtypes except refractory anemia (RA)
- Patient has a haploidentical family member that meets medical criteria for donation.
Eligibility for other transplant types:
- Patient considered likely to have clinical deterioration and rapid disease progression during an unrelated donor search, or
- Patient who has already had an unproductive donor search or
- Patient ineligible for or has refused autologous transplant
Adequate renal and hepatic function for age:
- Serum creatinine <2 x ULN
- Alanine aminotransferase (ALT, SGPT) x ULN
- Aspartate aminotransferase (AST, SGOT) x ULN
- Total bilirubin 5_2 x ULN except if bilirubin is elevated due to Gilbert's syndrome or hemolytic anemia
- Adequate cardiac and pulmonary function for age.
- ECOG Performance Status 0, 1, or 2 or Lansky performance scale >50% for patients <16 years of age.
- Voluntary witnessed written informed consent. Children will be asked for assent where appropriate.
- The patient, if female, must be post-menopausal, premenarcheal, or sterile, or if the patient is of childbearing potential, she must be practicing a method of birth control considered effective and medically acceptable by the investigator for a minimum of 1 month prior to study entry and at least 2 months after the study end.
- Patient must have undergone successful leukapheresis to obtain adequate antigen presenting cells.
- Any patient who enters the study in a relapse state, with evidence of end organ (pulmonary, renal, or hepatic) toxicity, or with recent recovery from infection, who may potentially have little benefit from this protocol, must have his/her eligibility status discussed with the Principal Investigator.
- Patient must have life expectancy of at least 12 weeks.
Exclusion Criteria
Eligibility for other transplant types:
- Patient has family donor who is matched or single antigen mismatched at HLA-A, HLA-B, HLA-DR, and HLA-DQ. Donorrecipient matching must be evaluated via both phenotype and genotype.
- Patient has available unrelated donor who is matched at HLA-A, HLA-B, and HLA-DR. Donor-recipient matching must be evaluated via both phenotype and genotype.
- Active uncontrolled infection (continued positive blood or soft tissue cultures despite appropriate antibiotic treatment)
- Positive 13-HCG in a female of childbearing potential
- Evidence of HIV infection or known HIV positive serology
- Any prior bone marrow transplant
- A peripheral blood differential count at the time of leukapheresis with greater than 25% blasts. This exclusion criterion is valid only for the first four patients enrolled.
- Patients with Fanconi's anemia
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:in vitro-treated bone marrow transplantation
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Incidence of primary graft failure
大体时间:up to 30 days post-transplant
|
up to 30 days post-transplant
|
次要结果测量
结果测量 |
大体时间 |
---|---|
Incidence of hyperacute GVHD
大体时间:up to 100 days post-transplant
|
up to 100 days post-transplant
|
Incidence of Grade D acute GVHD
大体时间:up to 50 days post-transplant
|
up to 50 days post-transplant
|
Incidence of adverse events
大体时间:up to 100 days post-transplant
|
up to 100 days post-transplant
|
合作者和调查者
调查人员
- 学习椅:Eva Guinan, MD、Dana-Farber Cancer Institute
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
- III期成人弥漫性大细胞淋巴瘤
- III期成人免疫母细胞大细胞淋巴瘤
- III期成人伯基特淋巴瘤
- IV期3级滤泡性淋巴瘤
- IV期成人弥漫性大细胞淋巴瘤
- IV期成人免疫母细胞大细胞淋巴瘤
- IV期成人Burkitt淋巴瘤
- 复发性 3 级滤泡性淋巴瘤
- 复发性成人弥漫性大细胞淋巴瘤
- 复发性成人免疫母细胞大细胞淋巴瘤
- 复发性成人伯基特淋巴瘤
- III期儿童小无裂细胞淋巴瘤
- IV期儿童小无裂细胞淋巴瘤
- IV期儿童大细胞淋巴瘤
- 复发性儿童小无裂细胞淋巴瘤
- 复发性儿童大细胞淋巴瘤
- 慢性粒单核细胞白血病
- 新生骨髓增生异常综合征
- 既往治疗过的骨髓增生异常综合征
- 继发性骨髓增生异常综合征
- 儿童急性淋巴细胞白血病处于缓解期
- 儿童急性髓性白血病处于缓解期
- 儿童骨髓增生异常综合征
- 复发性成人急性髓性白血病
- 缓解期成人急性髓性白血病
- 复发性成人霍奇金淋巴瘤
- 儿童免疫母细胞大细胞淋巴瘤
- 复发/难治性儿童霍奇金淋巴瘤
- 复发性成人弥漫性小裂细胞淋巴瘤
- 复发性成人弥漫性混合细胞淋巴瘤
- III期3级滤泡性淋巴瘤
- III期成人弥漫性小裂细胞淋巴瘤
- III期成人弥漫性混合细胞淋巴瘤
- IV期成人弥漫性混合细胞淋巴瘤
- II期多发性骨髓瘤
- III期多发性骨髓瘤
- I期成人弥漫性小裂细胞淋巴瘤
- 连续 II 期成人弥漫性小裂细胞淋巴瘤
- 非连续性 II 期成人弥漫性小裂细胞淋巴瘤
- I期多发性骨髓瘤
- 复发性成人淋巴母细胞淋巴瘤
- III期成人淋巴母细胞淋巴瘤
- IV期成人淋巴母细胞淋巴瘤
- 难治性多发性骨髓瘤
- 复发性成人急性淋巴细胞白血病
- 复发性儿童急性淋巴细胞白血病
- I期儿童大细胞淋巴瘤
- II期儿童大细胞淋巴瘤
- III期儿童大细胞淋巴瘤
- I期儿童淋巴母细胞淋巴瘤
- II期儿童淋巴母细胞淋巴瘤
- III期儿童淋巴母细胞淋巴瘤
- IV期儿童淋巴母细胞淋巴瘤
- I期儿童小无裂细胞淋巴瘤
- II期儿童小无裂细胞淋巴瘤
- 非连续性 II 期成人弥漫性大细胞淋巴瘤
- 非连续性 II 期成人弥漫性混合细胞淋巴瘤
- 非连续性 II 期成人淋巴母细胞淋巴瘤
- 非连续性 II 期 3 级滤泡性淋巴瘤
- 缓解期成人急性淋巴细胞白血病
- 复发性儿童急性髓性白血病
- 非连续性 II 期成人伯基特淋巴瘤
- 非连续性 II 期成人免疫母细胞大细胞淋巴瘤
- 复发性儿童淋巴母细胞淋巴瘤
- I期成人伯基特淋巴瘤
- 连续 II 期成人伯基特淋巴瘤
- 连续 II 期成人免疫母细胞大细胞淋巴瘤
- I期成人免疫母细胞大细胞淋巴瘤
- 儿童弥漫性大细胞淋巴瘤
- 连续 II 期 3 级滤泡性淋巴瘤
- I期3级滤泡性淋巴瘤
- 连续 II 期成人弥漫性大细胞淋巴瘤
- 连续II期成人弥漫性混合细胞淋巴瘤
- I期成人弥漫性大细胞淋巴瘤
- I期成人弥漫性混合细胞淋巴瘤
- 连续 II 期成人淋巴母细胞淋巴瘤
- I期成人淋巴母细胞淋巴瘤
- 难治性血细胞减少伴多系发育异常
- 移植物抗宿主病
其他相关的 MeSH 术语
- 病理过程
- 免疫系统疾病
- 组织学类型的肿瘤
- 肿瘤
- 淋巴增生性疾病
- 淋巴系统疾病
- 免疫增生性疾病
- 疾病
- 骨髓疾病
- 血液病
- 癌前病变
- 淋巴瘤
- 综合症
- 骨髓增生异常综合征
- 白血病
- 白血病前期
- 移植物抗宿主病
- 药物的生理作用
- 药理作用的分子机制
- 抗感染药
- 自主代理
- 周围神经系统药物
- 核酸合成抑制剂
- 酶抑制剂
- 抗炎药
- 抗风湿药
- 抗代谢药、抗肿瘤药
- 抗代谢物
- 抗肿瘤药
- 免疫抑制剂
- 免疫因素
- 止吐药
- 胃肠道药物
- 糖皮质激素
- 荷尔蒙
- 激素、激素替代品和激素拮抗剂
- 神经保护剂
- 保护剂
- 抗肿瘤药,烷基化
- 烷化剂
- 清髓性激动剂
- 皮肤病药物
- 微量元素
- 维生素
- 抗真菌剂
- 生殖控制剂
- 解毒剂
- 复合维生素B
- 堕胎药,非甾体
- 堕胎剂
- 叶酸拮抗剂
- 神经钙蛋白抑制剂
- 甲泼尼龙
- 环磷酰胺
- 亚叶酸
- 左旋叶酸
- 甲氨蝶呤
- 环孢菌素
- 环孢菌素
其他研究编号
- 99-205
- P30CA006516 (美国 NIH 拨款/合同)
- GENE-C9909-38
- NCI-G00-1801
- CDR0000067977 (其他标识符:other)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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环磷酰胺的临床试验
-
Tianjin Medical University Cancer Institute and...CSPC Ouyi Pharmaceutical Co., Ltd.尚未招聘