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

Phase 2

Completed

Interventions: Drug: cyclophosphamide
Drug: etoposide
Drug: rituximab
Drug: cytarabine
Drug: doxorubicin
Drug: tositumomab

Brief Summary: 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).

Detailed Description: 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

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Induction + Consolidation + Bexxar	etoposide	Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)
Induction + Consolidation + Bexxar	cyclophosphamide	Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)
Induction + Consolidation + Bexxar	cytarabine	Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)
Induction + Consolidation + Bexxar	rituximab	Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)
Induction + Consolidation + Bexxar	doxorubicin	Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)
Induction + Consolidation + Bexxar	tositumomab	Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)

Primary Outcome Measures

Name	Time	Method
1 Year Progression-free Survival Rate	1 year	Progression-free survival is measured from the first day of induction chemotherapy to the date of progression, relapse or death. Definitions of response criteria are as described by Cheson. Progressive Disease: \>50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PDs or nonresponders, appearance of any new lesion during or at the end of therapy.

Secondary Outcome Measures

Name	Time	Method
Disease-free Survival	10 years	Disease-free survival is measured from the date of CR or CRu to date of relapse or death
Overall Response	up to 1 year	Percent of subjects who achieved a complete response (CR) or partial response (PR) any time during the treatment period. CR = complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR = 1. \>/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. 2. No increase should be observed in the size of other nodes, liver, or spleen. 3. Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. 4. Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. 5. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders. 6. No new sites of disease should be observed.
Secondary Malignancies	10 years	The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes.
Overall Survival	10 years	Overall Survival is measured from the first day of chemotherapy until death from any cause.