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
Overview
- Phase
- Phase 2
- Intervention
- rituximab
- Conditions
- Lymphoma
- Sponsor
- City of Hope Medical Center
- Enrollment
- 122
- Locations
- 1
- Primary Endpoint
- 2-Year Progression-Free Survival
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: rituximab
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.
Intervention: carmustine
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.
Intervention: cytarabine
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.
Intervention: etoposide
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.
Intervention: melphalan
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.
Intervention: ASCT
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.
Intervention: yttrium Y 90 ibritumomab tiuxetan
Outcomes
Primary Outcomes
2-Year Progression-Free Survival
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
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 \[Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.\]
Secondary Outcomes
- 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)