A Phase II Study of Yttrium-90-Labeled Anti-CD20 Monoclonal Antibody in Combination With High-Dose Beam Followed by Autologous Stem Cell Transplantation for Poor Risk/Relapsed B-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- 2-Year Progression-Free Survival
研究概览
简要总结
This phase II clinical trial studies how well yttrium Y 90 ibritumomab tiuxetan, rituximab, and high-dose chemotherapy followed by peripheral blood stem cell transplant in treating patients with relapsed B-cell non-Hodgkin lymphoma. Monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving monoclonal antibody therapy, radioimmunotherapy (RIT), and high-dose combination chemotherapy before a peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin lymphoma.
详细描述
PRIMARY OBJECTIVE:
I. To estimate the 2-year progression free survival.
SECONDARY OBJECTIVES:
II. To estimate the 2-year overall survival.
III. To estimate the 2-year cumulative incidence of progression.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must have biopsy proven diagnosis of low- and intermediate-grade non-Hodgkin lymphoma (NHL) working formulation B, C,D, E, F, and G; including mantle cell lymphoma; patients with transformed lymphoma are also eligible
- •Demonstrated monoclonal CD20 positive b-cell population in lymph nodes and/or bone marrow
- •Patients must have relapsed after achieving a complete or partial response to prior therapy, have never responded to prior therapy or have poor risk disease
- •Patients with prior bone marrow involvement must have bone marrow aspiration and biopsy within 60 days prior to stem cell collection which shows =< 10% lymphomatous involvement of total cellularity; alternatively, patients with prior bone marrow involvement should have a normal bone marrow study which shows =< 10% lymphomatous involvement within 28 days before salvage chemotherapy
- •Normal renal function test with serum creatinine of < upper limit of normal (ULN), and a creatinine clearance of >= 60 ml/min (measured or calculated)
- •Adequate pulmonary function as measured by forced expiratory volume in 1 second (FEV1) > 60% of predicted measured, or a diffusion capacity of carbon monoxide (DLCO) >= 50% of predicted measured
- •Cardiac ejection fraction of > 50% by echocardiogram or multi gated acquisition (MUGA) scan; the left ventricular ejection fraction (LVEF) from the prestudy echocardiogram (ECHO) or MUGA may be used for eligibility purposes, even if the prestudy stress test indicated a lower LVEF
- •Adequate liver function tests with a bilirubin of =< 1.5 x ULN and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) =< 2 x ULN
- •Negative human immunodeficiency virus antibody
- •Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1; karnofsky performance status (KPS) >= 80
- •No active central nervous system (CNS) disease or prior history of CNS disease
- •Patients must have recovered from last therapy and should be at least four weeks from prior radiation or systemic chemotherapy on the day of administration of Y2B8
- •After the last systemic therapeutic chemotherapy (Cytoxan, administered only for stem cell mobilization is not considered therapeutic) and prior to initiation of high dose treatment, the patient should have a baseline computed tomography (CT) scan and positron emission tomography (PET) scan done; an fluorodeoxyglucose-computed tomography (FDG/CT) scan is sufficient, however, is clinically indicated, an additional diagnostic CT may be ordered; exception: if scans were done and were negative for disease just prior to priming chemotherapy (therapeutic or nontherapeutic) and subsequent stem cell harvest, they do not need to be repeated prior to initiation of high dose treatment
排除标准
- •Presence of human anti-Zevalin antibody (HAZA)
- •Prior radioimmunotherapy
- •Failure to collect adequate number of CD34+ cells >= 3 x 10^6/kg
- •Abnormal cytogenetic study not related to the underlying lymphoma on the bone marrow aspirate sample prior to stem cell collection; if cytogenetics were not performed on the marrow aspirate prior to stem cell collection, cytogenetics on the peripheral blood may be performed
- •Prior bone marrow transplantation
- •Prior malignancy except for:
- •Adequately treated basal cell or squamous cell skin cancer
- •Adequately treated noninvasive carcinoma
- •Other cancer from which the patient has been disease-free for at least five years
- •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
- •Patients who are pregnant or lactating
研究组 & 干预措施
Treatment (RIT, ZBEAM, ASCT)
RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan IV following rituximab IV on day -14. HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2; and melphalan IV on day -1. STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: rituximab (Biological)
Treatment (RIT, ZBEAM, ASCT)
RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan IV following rituximab IV on day -14. HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2; and melphalan IV on day -1. STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: carmustine (Drug)
Treatment (RIT, ZBEAM, ASCT)
RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan IV following rituximab IV on day -14. HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2; and melphalan IV on day -1. STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: cytarabine (Drug)
Treatment (RIT, ZBEAM, ASCT)
RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan IV following rituximab IV on day -14. HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2; and melphalan IV on day -1. STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: etoposide (Drug)
Treatment (RIT, ZBEAM, ASCT)
RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan IV following rituximab IV on day -14. HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2; and melphalan IV on day -1. STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: melphalan (Drug)
Treatment (RIT, ZBEAM, ASCT)
RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan IV following rituximab IV on day -14. HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2; and melphalan IV on day -1. STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: ASCT (Procedure)
Treatment (RIT, ZBEAM, ASCT)
RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan IV following rituximab IV on day -14. HIGH-DOSE COMBINATION CHEMOTHERAPY: Patients receive carmustine IV on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2; and melphalan IV on day -1. STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0. Patients also receive rituximab on day 8*. NOTE: * Some patients may also receive rituximab on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: yttrium Y 90 ibritumomab tiuxetan (Radiation)
结局指标
主要结局
2-Year Progression-Free Survival
时间窗: From peripheral stem cell infusion (Day0 ASCT) to first observation of progressive disease or death due to any cause, whichever comes first, assessed up to 5 years
Progression-free survival (PFS) was defined as time from peripheral stem cell infusion to recurrence, progression or death. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. Progression-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula \[Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.\]
次要结局
- 100-Day Treatment-Related Mortality(From peripheral stem cell infusion (Day0 ASCT) to death due to any couse, assessed up to 5 years)
- 2-Year Overall Survival(From peripheral stem cell infusion (Day0 ASCT) to death due to any cause, assessed up to 5 years)
- 2-Year Cumulative Incidence of Progression(From peripheral stem cell infusion (Day0 ASCT) to date of first observation of progressive disease or relapsed disease, assessed up to 5 years)
- Number of Patients With Active Disease at ASCT Achieving CR/PR by Day 100 After ASCT(Up to Day 100 post-ASCT)
- Number of Patients With Grade 3-4 Bearman Toxicities.(From initial of study treatment to Day 100 post-ASCT)
- Time to Neutrophil Recovery(From peripheral stem cell infusion (Day0 ASCT) till the first of 3 consecutive days of an absolute neutrophil count ≥ 500/µL.))
- Time to Platelet Recovery(From peripheral stem cell infusion (Day0 ASCT) till the first of 7 consecutive days with a platelet count ≥ 20,000/µL with no transfusions)
- Number of Patients With RIT/ZBEAM Developing Therapy Induced MDS and AML(From peripheral stem cell infusion (Day0 ASCT) to onset of therapy induced MDS/AML, assessed up to 5 years)