Rituximab and Combination Chemotherapy Combined With Yttrium Y 90 Ibritumomab Tiuxetan in Treating Older Patients With Previously Untreated B-Cell Lymphoma
Status and phase
Conditions
Treatments
Details and patient eligibility
About
RATIONALE: Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.
PURPOSE: Phase II trial to study the effectiveness of combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan in treating older patients who have B-cell lymphoma that has not been previously treated.
Full description
OBJECTIVES:
- Determine the progression-free and overall survival of patients age 60 and over with previously untreated diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combined with yttrium Y 90 ibritumomab tiuxetan.
- Determine the incidence of adverse experiences, hematologic toxicity (WBC, hemoglobin, and platelet nadirs; and transfusion requirements), cardiac toxicity (incidence of left ventricular dysfunction and cardiomyopathy by echocardiography), and the development of human antimouse antibody/human anti-chimeric antibody in patients treated with this regimen.
- Determine the predictive value of detecting minimal residual disease by molecular techniques for future relapse/recurrence in patients treated with this regimen.
- Determine the response rate of patients treated with this regimen.
- Determine the red blood cell transfusion requirements, change in hemoglobin from baseline, and incidence of anemia with prophylactic darbepoetin alfa support in patients treated with this regimen.
- Determine the conversion rate to complete remission in patients treated with ibritumomab tiuxetan who achieve a partial remission post-R-CHOP.
- Determine the effect of darbepoetin alfa on the quality of life of these patients.
OUTLINE: This is an open-label, nonrandomized study.
- Chemotherapy: Patients receive rituximab IV over 2-5 hours, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5 or 2-6; and filgrastim (G-CSF) subcutaneously (SC) on days 7-15. Patients also receive darbepoetin alfa SC on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Radioimmunotherapy: Patients receive rituximab IV over 3-5 hours and indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0.
Patients undergo gamma camera imaging at 2-24 hours and 48-72 hours after the injection of IDEC-In2B8 to observe the flow of ibritumomab tiuxetan. If the flow is deemed safe, then patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7.
Quality of life is assessed at baseline, before course 5 of chemotherapy, before radioimmunotherapy, and at 3 months.
Patients are followed every 3 months for 1 year and then every 6 months for 4 years.
PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
-
Histologically confirmed diffuse large B-cell lymphoma, including any of the following subtypes:
- Centroblastic
- Immunoblastic
- T-cell/histiocyte-rich
- Lymphomatoid granulomatosis type
- Anaplastic large B-cell
- Plasmablastic
- Mediastinal
- Intravascular large B-cell lymphoma
-
Previously untreated
-
High-intermediate or high-risk disease, defined by an age-adjusted international prognostic index score of 2 or 3 (with 1 point each assigned for a ECOG greater than 1/Karnofsky less than 80%, lactate dehydrogenase greater than normal, and stage III or IV)
-
Lymphomas with discordant histology and a diffuse large B-cell component are eligible
-
Must have an initial diagnostic specimen that is CD20+
-
At least Ann Arbor stage II disease
- No confinement of disease to an involved-field radiotherapy port (stage I or limited stage II disease)
-
Bidimensionally measurable disease with at least 1 lymph node at least 2.0 cm by 2.0 cm by physical examination, CT scan, or positron-emission tomography
-
Bone marrow cellularity greater than 15%
-
No known brain or leptomeningeal metastases
-
No primary effusion lymphomas
PATIENT CHARACTERISTICS:
Age
- 60 and over* NOTE: *Patients 60 to 65 years of age must be deemed ineligible for autologous stem cell transplantation
Performance status
- Karnofsky 50-100%
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- Bilirubin no greater than 2.0 mg/dL (except for Gilbert's disease)
Renal
- Creatinine no greater than 1.5 mg/dL* OR
- Creatinine clearance greater than 50 mL/min* NOTE: *Patients not meeting either criterion but who have renal insufficiency directly related to lymphomatous involvement of the kidneys or renal collecting system are allowed
Cardiovascular
- Cardiac ejection fraction at least 50% by echocardiogram
- No acute myocardial infarction within the past 3 months
- No uncontrolled hypertension
- No New York Heart Association class III or IV congestive heart failure
- No unstable angina pectoris
Other
-
Not pregnant or nursing
-
Fertile patients must use effective contraception
-
HIV negative
-
B12 and folate greater than the lower limit of normal
-
Transferrin saturation at least 15%
-
Ferritin greater than 10 µg/L
-
At least 6 weeks since prior RBC donation
-
No active seizure disorder
- Prior seizure disorder allowed if free of antiseizure medication and evidence of seizure activity for the past 5 years
-
No concurrent uncontrolled medical problems that would preclude administration of chemotherapy or radioimmunotherapy
-
No other concurrent malignancy treated with chemotherapy or radiotherapy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 4 weeks since prior RBC transfusion
- No prior biologic therapy
- No other concurrent biologic therapy
Chemotherapy
- No prior chemotherapy (one course of R-CHOP allowed)
- No other concurrent standard or investigational chemotherapy
Endocrine therapy
- No more than 7 consecutive days of prior steroids (premedication allowed for prior intravenous contrast allergy)
- No other concurrent corticosteroids
Radiotherapy
- No prior radiotherapy
Surgery
- Not specified
Trial design
Primary purpose
Allocation
Interventional model
Masking
65 participants in 1 patient group
Trial contacts and locations
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal