Dose-Intense Yttrium-90 Ibritumomab Tiuxetan (Zevalin)-Containing Non-Myeloablative Conditioning for Allogeneic Stem Cell Transplantation in B-cell Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Treatment-Related Mortality (TRM)
研究概览
简要总结
The goal of this clinical research study is to learn if adding Zevalin (ibritumomab tiuxetan) to low-intensity chemotherapy (the combination of rituximab, bendamustine, and fludarabine), followed by an allogeneic stem cell transplant, can help to control lymphoma. The safety of this combination will also be studied.
Two (2) forms of ibritumomab tiuxetan will be used in this study. 90Y-ibritumomab tiuxetan is designed to attach to lymphoma cells and destroy the cells using a radioactive particle that is attached to it. 111In-ibritumomab tiuxetan is like 90Y- ibritumomab tiuxetan, but the radioactive particle that is attached to it does not kill lymphoma cells. The radioactive particle makes the drug able to be seen inside your body. It is being used in this study to predict how fast the study drug will travel in the body and how long the drug stays in the body.
Rituximab is designed to attach to lymphoma cells, which may cause them to die.
Bendamustine is designed to damage and destroy the DNA (genetic material) of cancer cells.
Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.
详细描述
Study Drug Administration and Procedures:
The chemotherapy, some of the other drugs in this study, and the stem cell transplant will be given by vein through your central venous catheter (CVC). A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia and will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form. Blood samples will also be drawn through the CVC.
On Days -22 (22 days before you receive the stem cell transplant), you will receive rituximab by vein over 3-4 hours. You will then receive 111In-ibritumomab tiuxetan by vein over 30 minutes.
From Day -22 through Day -16, you will have scans called whole-body planar scintigraphy imaging. In these scans, a special camera will capture 2-dimensional images of the whole body to see where the radioactive 111In- ibritumomab tiuxetan that was injected on Day -22 has spread. No additional radiation will be used in this scan. Scintigraphy will be performed right after the injection, then 3-6 hours after the injection, then 24, 72, and 144 hours (+/- 2 hours) after the injection.
After the last scintigraphy imaging scan, the scans will be reviewed to learn how much radiation has traveled to different organs and to decide how much 90Y- ibritumomab should be used.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 to 70 years of age.
- •Patients with the following CD20+ lymphoid malignancies who are eligible for allogeneic transplantation: a. Relapsed or refractory follicular lymphoma; b. Relapsed or refractory or high risk mantle cell lymphoma (hi ki67; blastic); c. Recurrent or refractory marginal zone; d. Recurrent or refractory CLL/small lymphocytic lymphoma; e. Double-hit lymphoma; f. Diffuse large B cell lymphoma; g. Richter's patients; or h. Refractory or recurrent Burkitts.
- •Patients who meet criterion #2 or have any of the following are eligible: a. Less than PR to salvage chemotherapy; b. Kinetic failure; c. Having received more than 3 lines of therapy; d. Failure to mobilize autologous stem cell; e. 10% or more marrow involvement; f. 6 months post autologous stem cell transplant.
- •Patients must have a fully-matched related donor or a matched unrelated donor identified. Double cord (at least 4/6 matched) can be used if no adult matched donor is available.
- •Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.
- •Left ventricular EF >/= 45% with no uncontrolled arrythmias or symptomatic heart disease.
- •FEV1, FVC >/= 60% and corrected DLCO >/= 60%.
- •Serum creatinine </=1.6 mg/dL. Serum bilirubin < 2 mg/dL (unless due to Gilbert's Syndrome).
- •SGPT < 2 X upper limit of normal.
- •Men and women of reproductive potential must agree to follow accepted birth control methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- •Negative Beta HCG test within 30 days in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization). Pregnancy testing is not required for post-menopausal or surgically sterilized women.
排除标准
- •Patient with active CNS involvement with lymphoid malignancy.
- •Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
- •Patients with other malignancies diagnosed within 2 years prior to study registration. Skin squamous or basal cell carcinoma are exceptions.
- •Active bacterial, viral or fungal infections.
- •History of stroke within 6 months prior to study registration.
- •A prior allogeneic stem cell transplant.
- •Patient has received other investigational drugs within 3 weeks before study registration.
- •Presence of circulating malignant lymphoid cells or bone marrow with lymphoma that constituted more than 25% of the cellular elements.
- •Serious nonmalignant or malignant disease or psychiatric illness, which, in the opinion of the investigator would compromise protocol objectives or interfere with participation.
- •Patients who are breast-feeding.
研究组 & 干预措施
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Rituximab (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: 111In Ibritumomab (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Planar Scintigraphy Imaging (Procedure)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: 90Y IbritumomabTiuxetan (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Fludarabine (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Bendamustine (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Thymoglobulin (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Tacrolimus (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Methotrexate (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Mycophenolate (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: G-CSF (Drug)
Yttrium-90 Ibritumomab + Chemo
Day -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
干预措施: Stem Cell Transplantation (Procedure)
结局指标
主要结局
Treatment-Related Mortality (TRM)
时间窗: 100 days
Number of participants without treatment related mortality at day 100.
次要结局
- Overall Survival (OS)(From date of treatment to date of relapse or death, up to 3 years)