Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma
Condition: Large B Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell
Intervention: rituximab; cyclophosphamide; doxorubicin; vincristine; prednisone; etoposide; filgrastim; pegfilgrastim
Intervention description: IV; IV; IV or CIVI; IV or CIVI; oral; CIVI; IV; IV
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Etoposide; Vincristine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 524.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies rituximab when given together with two different
      combination chemotherapy regimens to compare how well they work in treating patients with
      diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, may
      block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy
      work in different ways to stop the growth of cancer cells, either by killing the cells, by
      stopping them from dividing, or by stopping them from spreading. Giving rituximab together
      with combination chemotherapy may kill more cancer cells. It is not yet known which
      combination chemotherapy regimen is more effective when given with rituximab in treating
      diffuse large B-cell non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying rituximab when given together with two
      different combination chemotherapy regimens to compare how well they work in treating
      patients with diffuse large B-cell lymphoma.
    

Eligibility criteria:

        1. Histologically documented de novo CD20+ DLBCL with stage II, III or IV disease.

               -  Stage I primary mediastinal (thymic) DLBCL is also eligible.

               -  Patients with an underlying low-grade lymphoma, such as a transformed lymphoma or
                  low-grade lymphoma in the bone marrow, are not eligible.

               -  Diagnosis should be based on an adequate tissue sample, including open biopsy or
                  core needle biopsy.

               -  Needle aspiration for primary diagnosis is unacceptable.

               -  Patients must have one of the following WHO classification subtypes:

                    -  Diffuse large B-cell lymphoma (includes morphological variants:
                       centroblastic, immunoblastic, T-cell/histiocyte rich, and anaplastic)

                    -  Mediastinal (thymic) large B-cell lymphoma

                    -  Intravascular large B-cell lymphoma

               -  Note: Failure to submit a pathology block within 60 days of patient registration
                  will be considered a major protocol violation.

                    -  Fresh (frozen) tumor biopsy must be available or attempted. A frozen tumor
                       biopsy equivalent to a minimum of four at least 16 gauge needle cores is an
                       important component of this study.

                    -  Patients without adequate frozen material should have a biopsy performed to
                       obtain material.

                    -  If a biopsy is performed and does not yield adequate material, the patient
                       is still eligible for the study. If a biopsy cannot be done safely, the
                       patient may still be eligible for the study if permission is granted.

               -  Note: This study does not allow concurrent radiation unless a patient has a
                  documented CNS treatment failure with no systemic failure.

          2. No prior cytotoxic chemotherapy or rituximab. Patients may be entered if they have
             received prior limited field radiation therapy or a short course of glucocorticoids (<
             10 days) for an urgent local disease complication at diagnosis (e.g., cord
             compression, SVC syndrome). Patients who have received chemotherapy for prior
             malignancies are not eligible.

          3. Age ≥ 18 years

          4. ECOG Performance Status 0-2

          5. No active ischemic heart disease or congestive heart failure. If there is suspicion of
             cardiac disease, a cardiac ejection fraction must show LVEF > 45%, but the study is
             not required

          6. No known lymphomatous involvement of the CNS. A lumbar puncture prior to study is not
             required in the absence of neurological symptoms

          7. No known HIV disease. Patients with a history of intravenous drug abuse or any other
             behavior associated with an increased risk of HIV infection should be tested for
             exposure to the HIV virus. Patients who test positive or who are known to be infected
             are not eligible.

          8. Non pregnant and non-nursing. Treatment would expose an unborn child to significant
             risks. Women and men of reproductive potential should agree to use an effective form
             of contraception.

          9. Patients with active medical processes (e.g., uncontrolled bacterial or viral
             infection, bleeding) not related to their lymphoma should be excluded.

         10. Required Initial Laboratory Values (unless non-Hodgkin lymphoma):

               -  ANC ≥ 1000/μL

               -  Platelets ≥ 100,000/μL

               -  Creatinine≤ 1.5 mg/dL or creatinine clearance ≥ 50 cc/min

               -  Total Bilirubin ≤ 2 mg/dL (unless a history of Gilbert's Disease)