Rituximab and Combination Chemotherapy Combined With Yttrium Y 90 Ibritumomab Tiuxetan in Treating Older Patients With Previously Untreated B-Cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Intervention: darbepoetin alfa; filgrastim; rituximab; cyclophosphamide; doxorubicin hydrochloride; prednisone; vincristine sulfate; indium In 111 ibritumomab tiuxetan; yttrium Y 90 ibritumomab tiuxetan
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine; Darbepoetin alfa; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 60 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: noncontiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma

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.
    

Eligibility 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