Phase III Rituxan/BEAM vs. Bexxar/BEAM With Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Persistent or Relapsed Chemotherapy Sensitive Diffuse Large B-cell Non-Hodgkin's Lymphoma (BMT CTN #0401)

Inclusion Criteria:

- Diagnosis of persistent or recurrent REAL classification diffuse large B-cell
lymphoma, composite lymphoma with more than 50% diffuse large B-cell lymphoma,
mediastinal B-cell lymphoma

- Demonstration of CD20+ on at least one histologic specimen

- 18-80 years old at time of first registration

- Three or fewer prior regimens of chemotherapy over the entire course of their disease
treatment (including one induction chemotherapy and no more than 2 salvage
chemotherapies); monoclonal antibody therapy and involved field radiation therapy
will not be counted as prior therapies

- Disease status of primary induction failure, first relapse, or second complete
remission; all patients must have chemosensitive disease as demonstrated by response
to induction or salvage chemotherapy with at least a partial response (as defined in
the protocol)

- No more than a 20% bone marrow involvement

- Patients with adequate organ function as measured by:

- Cardiac: American Heart Association Class I: Patients with cardiac disease but
without resulting limitation of physical activity; ordinary physical activity does
not cause undue fatigue, palpitation, dyspnea, or anginal pain; additionally,
patients greater than 60 years of age must have a left ventricular ejection fraction
at rest of at least 40% demonstrated by MUGA

- Hepatic: Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia
attributed to Gilbert syndrome) and ALT and AST less than 3x the upper limit of
normal

- Renal: Creatinine less than 2.0 mg/dL or creatinine clearance (calculated creatinine
clearance is permitted) more than 40 mL/min; no hydronephrosis on CT scan prior to
mobilization

- Pulmonary: DLCO, FEV1, FVC at least 45% of predicted (corrected for hemoglobin)

- Autologous graft with a minimum of at least 1.5 X 10^6 CD34+ cells/kg (target greater
than 2.0 X 10^6 CD34+ cells/kg. Peripheral blood stem cells (PBSC) are preferred;
however, if PBSC mobilization fails, cells can be obtained by institutional practices
(in cases where bone marrow will be used for transplantation, the required CD34+ dose
does not apply and institutional practice for total nucleated cell dose should be
used).

- Initiate conditioning therapy within 3 months of mobilization

- Signed informed consent

Exclusion Criteria:

- Karnofsky performance score less than 70%

- Transformed follicular lymphoma

- Uncontrolled bacterial, viral, or fungal infection (currently taking medication and
with progression or no clinical improvement)

- Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma
in situ; cancer treated with curative intent less than 5 years previously will not be
allowed unless approved by the Medical Monitor or Protocol Chair; cancer treated with
curative intent less than 5 years previously will be allowed

- Pregnant (positive β-HCG) or breastfeeding; this patient population is excluded due
to the lack of data on the use of Bexxar in patients who are pregnant or
breastfeeding

- Seropositivity for HIV; this patient population is excluded due to the lack of data
on the use of Bexxar in HIV positive patients and because the treatment regimens are
too immunosuppressive for this patient population

- Fertile men or women unwilling to use contraceptive techniques from the time of
initiation of mobilization until six-months post-transplant

- Prior autologous or allogeneic HSCT

- Patients with evidence of MDS/AML or abnormal cytogenetic analysis indicative of MDS
on the pre-transplant bone marrow examination

- Patients with a prior severe reaction to Rituxan or G-CSF. Patients with severe
reactions to G-CSF that receive pre-medication for control of the reaction are not
excluded from study.

- Patients who have received prior radioimmunotherapy

- Patients with known hypersensitivity to murine proteins