Chemotherapy With Monoclonal Antibody and Radioimmunotherapy for High-Risk B-Cell Non-Hodgkins Lymphoma

• Disease-free Survival in Patients With a Complete Response (CR or CRu) [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  Disease-free survival is measured from the date of CR or CRu to date of relapse or death
• Overall Survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  Overall Survival is measured from the first day of chemotherapy until death from any cause.
• Overall Response [ Time Frame: During the treatment period ] [ Designated as safety issue: No ]
  Number of patients who achieved a complete response (CR or CRu) or partial response as defined by Cheson criteria,at any time during the treatment period.
• Secondary Malignancies [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
  The number of patients who develop a secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes.

The purpose of this study is to determine whether using high-dose chemotherapy, monoclonal antibodies, and targeted radioimmunotherapy will slow the progression of disease in patients with high-risk Non-Hodgkin's Lymphoma (NHL).

This is a phase II efficacy trial for patients with untreated, high-risk, B-cell Non-Hodgkin's Lymphoma. The study will evaluate the efficacy and safety of high-dose chemotherapy combined with monoclonal antibodies and targeted radioimmunotherapy in previously untreated patients with high-risk NHL

• Drug: cyclophosphamide
  1.5g/m2 IV over 1 hour on days 1-4 of induction for a total dose of 6.0g/m2
  Other Name: Cytoxan®
• Drug: etoposide
  300mg/m2 IV over 1 hour every 12 on days 1-3 of induction for a total dose of 1.8 g/m2.
  Other Name: VP-16
• Drug: rituximab
  375mg/m2 each week x 4 weeks of induction, beginning on day 1
  Other Name: Rituxan
• Drug: cytarabine
  3g/m2 IV over 1 hour every 12 during consolidation for a total of 8 doses
  Other Name: Ara-C
• Drug: doxorubicin
  45mg/m2/day IV over 30 minutes on days 1, 2, 3 during consolidation
  Other Name: Adriamycin
• Drug: tositumomab
  450mg unlabeled tositumomab over 1 hour, followed by 5 millicurie (mCi) Iodine I-131 labeled tositumomab over 20 minutes on day 0. Therapeutic dose of labeled tositumomab will be administered on day 15.
  Other Name: Bexxar

Inclusion Criteria:

• Untreated, biopsy proven B-cell non-Hodgkin's lymphoma
• Age >/= 18 years
• No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for one year. The patient cannot have been exposed to chemotherapy to treat any of these diseases for at least 3 years prior to study entry.
• Meet staging studies and laboratory tests prior to induction, consolidation and radioimmunotherapy.

Exclusion Criteria:

• Significant medical and/or psychiatric illness which may compromise planned treatment;
• Pregnant or lactating;
• HIV-infection.
• Patients with follicular lymphoma grade 1, 2 or 3A are not eligible for this trial.