Phase I-II Non-Randomized Study of Yttrium 90 Ibritumomab Tiuxetan (Zevalin) With Non Myeloablative Allogeneic Stem Cell Transplantation in Patients With Relapsed, Refractory, or Transformed Indolent Non Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Engraftment, chimerism, transplant related toxicity, acute and chronic GVHD
研究概览
简要总结
The purpose of this study is to investigate the ability to combine a radioactive medication directly targeted against lymphoma cells with the immune effects of an allogeneic blood stem cell transplant.
详细描述
Despite initial high response rates of low grade Non Hodgkin lymphoma, progressive or refractory disease currently remains incurable. Being a radiosensitive tumor, we hypothesize that combining different modalities of treatment including targeted radioimmunotherapy (RIT), and a graft versus lymphoma effect related to an allogeneic non myeloablative stem cell transplant may increase response and survival rates in a safe manner in patients with persistent disease following initial treatment. In this study patients who are not eligible for a standard stem cell transplant approach because of relapsed or refractory disease and who have a related sibling donor are treated with RIT followed by an allogeneic non myeloablative blood stem cell transplant
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have/be
- •Age 18 to 65 years. Patients between age 66 and 69 may be enrolled if judged to be in excellent physical condition as per treating physician and study investigator and based on institutional practice.
- •Diagnosis of Non-Hodgkin lymphoma, follicular, marginal zone, small lymphocytic lymphoma, mantle cell lymphoma or transformed from an indolent NHL to aggressive histology disease lymphoma as defined by the World Health Organization.
- •Disease relapsed after, refractory or failing to achieve a PR after two or more cycles of intensive salvage chemotherapy (R-ESHAP or other) or disease relapsed after autologous stem cell transplantation. Poor partial response is defined as less than 50% reduction of tumor size. Salvage chemotherapy has to be administered after either 1st, 2nd or 3rd relapse
- •Disease expressing the CD 20 antigen
- •ECOG performance status 0-2
- •Judged to be able to tolerate NST and Zevalin treatment based on institutional criteria.
- •Signed written informed consent
- •At least one fully HLA matched sibling without evident contraindications to the donation procedures and willing to sign consent for donation
排除标准
- •Patients must not have/be
- •Abnormal renal function (creatinine > 1.5 x upper limit of normal (ULN)
- •Abnormal hepatic function (bilirubin > 2 x ULN, ALT/AST>2x ULN)
- •Cardiac ejection fraction <40% and/or other significant cardiac compromise
- •Severe defects in pulmonary function tests or receiving continuous oxygen
- •Severe concurrent illness, such as symptomatic congestive heart failure, severe arrhythmias, uncontrolled hypertension, diabetes, severe neurologic or psychiatric disorder or known HIV positive
- •Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) that may impact on patients life expectancy or any cancer curatively treated < 3 years prior to study entry.
- •History of prior allogeneic bone marrow transplant
- •Evidence of active hepatitis B or C infection or positivity for hepatitis-B surface antigen
- •Known type 1 hypersensitivity or anaphylactic proteins to any component of the Zevalin therapy or a history or presence of human anti-mouse antibodies (HAMA)
- •A female patient who is pregnant or breast feeding and an adult of reproductive potential who is not employing an effective method of birth control during the study.
- •CNS lymphoma
- •Ongoing confirmed or suspected significant infection
- •Prior treatment with radioimmunotherapy
- •Other condition preventing participation in standard NST
- •No fully matched sibling donor
研究组 & 干预措施
T
干预措施: Rituximab (Drug)
T
干预措施: 90Y ibritumomab tiuxetan (Zevalin) (Drug)
T
干预措施: Cyclophosphamide (Drug)
T
干预措施: Fludarabine (Drug)
T
干预措施: Non myeloablative allogeneic stem cell transplantation (Other)
结局指标
主要结局
Engraftment, chimerism, transplant related toxicity, acute and chronic GVHD
时间窗: one year
次要结局
- Overall response rate, overall and disease free survival(360 days)