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.
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. IV. To estimate time to hematopoietic recovery, using absolute neutrophil and platelet engraftment. V. To estimate incidence of grade 3-4 toxicities by Bearman Scale, Day 0 to Day 100. VI. To estimate the response rate (CR/PR). VII. To estimate 100-day treatment related mortality. VIII. To estimate incidence of myelodysplasia and therapy related acute myeloid leukemia (AML). IX. To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population treated with chemotherapy alone. OUTLINE: RADIOIMMUNOTHERAPY: Patients receive yttrium Y 90 ibritumomab tiuxetan intravenously (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 (BID) and cytarabine IV over 2 hours BID 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. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
122
Given IV
Given IV
Given IV
Given IV
Given IV
Undergo autologous peripheral blood stem cell transplant
Given IV
City of Hope Medical Center
Duarte, California, United States
2-Year Progression-Free Survival
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 \[Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.\]
Time frame: 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
2-Year Overall Survival
Overall survival (OS) was measured from peripheral stem cell infusion to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. \[Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.\]
Time frame: From peripheral stem cell infusion (Day0 ASCT) to death due to any cause, assessed up to 5 years
2-Year Cumulative Incidence of Progression
The cumulative incidence was estimated after taking into account the competing risk of early death.
Time frame: 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
Responses are assessed using the Revised Criteria for Malignant Lymphoma Response Definitions for Clinical Trials (Cheson et al. 2007). Complete Response (CR) defined as disappearance of all evidence of disease. Partial Response (PR) defined as regression of measurable disease and no new sites.
Time frame: Up to Day 100 post-ASCT
Number of Patients With Grade 3-4 Bearman Toxicities.
Toxicities were recorded using the modified Bearman Scale for non-hematologic adverse events.
Time frame: From initial of study treatment to Day 100 post-ASCT
100-Day Treatment-Related Mortality
The cumulative incidence was estimated after taking into account the competing risk of relapse post-ASCT.
Time frame: From peripheral stem cell infusion (Day0 ASCT) to death due to any couse, assessed up to 5 years
Time to Neutrophil Recovery
Neutrophil recovery was defined as the first of 3 consecutive days of an absolute neutrophil count ≥ 500/µL.
Time frame: 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
Platelet recovery was defined as the first of 7 consecutive days with a platelet count ≥ 20,000/µL with no transfusions.
Time frame: 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
Patient receiving the full treatment of RIT/ZBEAM developed therapy induced MDS or AML.
Time frame: From peripheral stem cell infusion (Day0 ASCT) to onset of therapy induced MDS/AML, assessed up to 5 years
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