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

Study Overview
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Brief Summary
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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
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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

Official Title
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Dose-Intensive Chemotherapy Combined With Monoclonal Antibody Therapy and Targeted Radioimmunotherapy for Untreated Patients With High-Risk B-Cell Non-Hodgkin's Lymphoma

Conditions
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Lymphoma, B-Cell

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: etoposide
* Drug: rituximab
* Drug: cytarabine
* Drug: doxorubicin
* Drug: tositumomab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction + Consolidation + Bexxar<br>Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab) | Drug: cyclophosphamide<br>* 1.5g/m2 IV over 1 hour on days 1-4 of induction for a total dose of 6.0g/m2<br>* Other names: Cytoxan®;Drug: etoposide<br>* 300mg/m2 IV over 1 hour every 12 on days 1-3 of induction for a total dose of 1.8 g/m2.<br>* Other names: VP-16;Drug: rituximab<br>* 375mg/m2 each week x 4 weeks of induction, beginning on day 1<br>* Other names: Rituxan;Drug: cytarabine<br>* 3g/m2 IV over 1 hour every 12 during consolidation for a total of 8 doses<br>* Other names: Ara-C;Drug: doxorubicin<br>* 45mg/m2/day IV over 30 minutes on days 1, 2, 3 during consolidation<br>* Other names: Adriamycin;Drug: tositumomab<br>* 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.<br>* Other names: Bexxar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 Year Progression-free Survival Rate | 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival | Disease-free survival is measured from the date of CR or CRu to date of relapse or death | 10 years | 
| Overall Survival | Overall Survival is measured from the first day of chemotherapy until death from any cause. | 10 years | 
| Overall Response | 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 = >/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders. No new sites of disease should be observed. | up to 1 year | 
| Secondary Malignancies | The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes. | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high risk non-hodgkins lymphoma, NHL, Bexxar, high dose chemotherapy