SPINOZA / שפינוזה. Study With Preparatory INduction Of Zevalin in Aggressive Lymphoma. A Randomized Phase 3 Study of BEAM Versus 90Yttrium Ibritumomab Tiuxetan (Zevalin) / BEAM in Patients Requiring ASCT for Relapsed DLBCL
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Overall Survival
研究概览
简要总结
This randomized phase III trial studies 90-yttrium ibritumomab tiuxetan and combination chemotherapy compared with combination chemotherapy alone before stem cell transplant in treating patients with diffuse large b-cell non-Hodgkin lymphoma that has returned after a period of improvement. Radioactive substances linked to monoclonal antibodies, such as 90-yttrium ibritumomab tiuxetan, can bind to cancer cells and give off radiation which may help kill cancer cells. Drugs used in chemotherapy, such as carmustine, etoposide phosphate, cytarabine, and melphalan (BEAM), work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether 90-yttrium ibritumomab tiuxetan and BEAM before a stem cell transplant are more effective than BEAM alone in treating patients with diffuse large b-cell non-Hodgkin lymphoma.
详细描述
PRIMARY OBJECTIVES: I. To compare overall survival (OS) between the two transplant arms, with at least a two year of follow-up. SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS), complete response (CR) and partial response (PR) proportion at day 100, time to hematopoietic recovery, incidence of infection, grade III-IV toxicities, treatment-related mortality, incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML).
OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive rituximab intravenously (IV) on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours twice daily (BID) on days -5 to -2; etoposide IV over 1 hour BID or once daily (QD) on days -5 to -2; and melphalan IV on day -1. Patients then undergo peripheral blood stem cell (PBSC) transplant on day 0. ARM II: Patients receive BEAM as in Arm I and undergo PBSC transplant on day 0.
After completion of study treatment, patients are followed up weekly for 30 days, 100 days, 6 months, 1 year, every 3 months for 1 year, and then annually for 3 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a pathological biopsy report.
- •Patients who are candidates for autologous stem-cell transplantation due to primary refractory or first relapse of disease.
- •Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy.
- •Patients with adequate autologous stem cell collection for transplantation (target >= 2.5 x 10^6 CD34+ cells/kg).
- •Patients must sign written informed consent.
- •Adequate birth control in fertile patients.
- •All prior chemotherapy completed at least three weeks before study treatment.
- •Marrow involvement less than 25% at transplantation, no limitation on blood counts (low platelet count allowed).
- •Negative HIV antibody.
排除标准
- •Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy.
- •Two or more relapses after initial response to induction chemotherapy.
- •High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with "De Novo" Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent to all other selection criteria.
- •Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit.
- •Creatinine > 2.0 mg/dl.
- •Uncontrolled infection.
- •Pregnancy or lactation.
- •Abnormal lung diffusion capacity (DLCO < 40% predicted).
- •Severe cardiovascular disease; New York Heart Association (NYHA) Functional Classification ≥
- •Active CNS disease involvement.
- •Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated for Stage I or II cancers are eligible provided they have a life expectancy > 5 years in relation to this prior malignance. The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer.
- •Pleural effusion or ascites > 1 liter.
- •Known hypersensitivity to rituximab.
- •Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate.
- •Prior radioimmunotherapy.
- •Prior autologous or allogeneic HSCT.
- •Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive.
- •Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume.
- •Patients who have received >500cGy radiation to the kidneys will be excluded from the study.
研究组 & 干预措施
Arm I (ZBEAM)
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: 90-Yttrium Ibritumomab tiuxetan (Radiation)
Arm I (ZBEAM)
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Carmustine (Drug)
Arm I (ZBEAM)
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Etoposide (Drug)
Arm I (ZBEAM)
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Cytarabine (Drug)
Arm I (ZBEAM)
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Melphalan (Drug)
Arm I (ZBEAM)
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Autologous Hematopoietic Stem Cell Transplant (Procedure)
Arm I (ZBEAM)
Patients receive rituximab IV on days -21 and -14, and 90-yttrium ibritumomab tiuxetan IV on day -14. Patients also receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Rituximab (Biological)
Arm II (BEAM)
Patients receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Carmustine (Drug)
Arm II (BEAM)
Patients receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Etoposide (Drug)
Arm II (BEAM)
Patients receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Cytarabine (Drug)
Arm II (BEAM)
Patients receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Melphalan (Drug)
Arm II (BEAM)
Patients receive BEAM comprising carmustine IV over 4 hours on day -6; cytarabine IV over 2 hours BID on days -5 to -2; etoposide IV over 1 hour BID or QD on days -5 to -2; and melphalan IV on day -1. Patients then undergo autologous hematopoietic stem cell transplant on day 0.
干预措施: Autologous Hematopoietic Stem Cell Transplant (Procedure)
结局指标
主要结局
Overall Survival
时间窗: Measured from randomization to date of death or last follow up date, whichever occurs first, for up to 5 years post randomization
Survival estimates will be calculated using the Kaplan-Meier method
次要结局
- Time to Progression(Up to 5 years)
- Number of Patients With Complete or Partial Response at Day 30(Day 0 to Day +30 post-HCT)
- Incidence of Infection(Day 0 to Day +100 post-HCT)
- Incidence of Non-relapse Mortality (NRM) Defined as Death Occurring in a Patient From Causes Other Than Relapse or Progression(From randomization until non-disease related death, or last follow-up, whichever comes first, assessed up to 5 years)
- Progression-free Survival(Measured from randomization until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up whichever comes first, for up to 5 years post randomization)
- Time to Neutrophil Engraftment(Day 0 to Day 100 post-HCT)
- Time to Platelet Engraftment(Day 0 to Day 100 post-HCT)
- Number of Patients With Grade 3-5 Toxicities Graded by the NCI CTCAE Version 4.0(Day -21 to Day +100 post-HCT)
- Cumulative Incidence of New, Abnormal Cytogenetics(Day 0 to Year 5 post-HCT)
- Cumulative Incidence of Secondary Malignancies(Up to 5 years)