Lymphoma
Conditions
Keywords
noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma
Brief summary
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.
Detailed 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.
Interventions
RADIATIONindium In 111 ibritumomab tiuxetan
BIOLOGICALdarbepoetin alfa
BIOLOGICALfilgrastim
BIOLOGICALrituximab
DRUGcyclophosphamide
DRUGdoxorubicin hydrochloride
DRUGvincristine sulfate
DRUGprednisone
RADIATIONyttrium Y 90 ibritumomab tiuxetan
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years | — |
| Progression-free Survival | 2 years | — |
| Event-free Survival | 2 years | — |
| Incidence of Adverse Experiences | 2 years | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Conversion Rate to Complete Remission | 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| R-CHOP and Ibritumomab Tiuxetan (Zevalin) 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. | 65 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not treated | 2 |
Baseline characteristics
| Characteristic | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
|---|---|
| Age, Continuous | 75 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 57 Participants |
| Region of Enrollment United States | 65 Participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 32 / 65 |
| other Total, other adverse events | 41 / 65 |
| serious Total, serious adverse events | 34 / 65 |
Outcome results
Primary
Event-free Survival
Time frame: 2 years
Population: Data were not collected
Primary
Incidence of Adverse Experiences
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.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| R-CHOP and Ibritumomab Tiuxetan (Zevalin) | Incidence of Adverse Experiences | 65 Participants |
Primary
Overall Survival
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| R-CHOP and Ibritumomab Tiuxetan (Zevalin) | Overall Survival | Dead | 32 Participants |
| R-CHOP and Ibritumomab Tiuxetan (Zevalin) | Overall Survival | Alive | 33 Participants |
Primary
Progression-free Survival
Time frame: 2 years
Population: Data were not collected
Secondary
Conversion Rate to Complete Remission
Time frame: 2 years
Population: Data were not collected