Molecular Risk Assessment in Planning Treatment for Patients With Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Analyzing genes that are present in cancer cells may be useful as a method for predicting the response of non-Hodgkin's lymphoma to cancer treatment. Imaging procedures such as positron emission tomography (PET) scans may improve the ability to measure how well cancer has responded to treatment. PURPOSE: This phase II trial is studying molecular risk assessment to see how well it works in predicting response to therapy in patients who are receiving treatment for non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine whether molecular risk assessment can identify groups of patients with diffuse large B-cell non-Hodgkin's lymphoma (NHL) who will demonstrate at least 50% difference in early response rates to treatment as determined by positron-emission tomography (PET) imaging. Determine, by PET imaging, the response rate of patients treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab. Determine whether early response rates can be predicted by gene expression profiles at diagnosis in these patients. Compare gene expression profiles of patients with refractory or relapsed large cell NHL with profiles of the disease at diagnosis. Determine relapse-free and overall survival rates of these patients. Determine the feasibility of a new NHL treatment algorithm based on prognostic index and molecular risk, and early response assessment by PET imaging. OUTLINE: Molecular risk assessment is performed using lymph node tissue from initial diagnosis to test for activated genes before starting treatment. Patients receive rituximab IV over 3-6 hours, cyclophosphamide IV over 30 minutes, doxorubicin IV over 5 minutes, and vincristine IV over 5 minutes on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for 3-8 courses. Patients undergo whole-body positron-emission tomography (PET) scanning at baseline and after course 3 to determine response. Results from the genetic testing and PET scans are used to determine further treatment recommendations. Patients are followed every 3 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 36-50 patients will be accrued for this study.

Official Title
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Molecular Risk Guided Treatment Of Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate
* Genetic: microarray analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma CD20 and/or CD19 positive by immunohistochemistry or flow cytometry Disease evaluable by positron-emission tomography scan Diagnostic tissue (either frozen or fresh unfixed) available for molecular testing or willing to undergo a repeat procedure to obtain such tissue No CNS involvement by lymphoma PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin no greater than 3 mg/dL Renal Creatinine no greater than 3 mg/dL Cardiovascular LVEF at least 40% Other Not pregnant or nursing Fertile patients must use effective contraception No significant organ dysfunction that would preclude study chemotherapy HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy No prior biological response modifier therapy Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy No prior radioimmunotherapy Surgery Not specified

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

| Intervention/Treatment |
| --- |
|Biological: rituximab|Rituximab IV over 3-6 hours.Treatment repeats every 21 days for 3-8 courses.|
|Drug: cyclophosphamide|Cyclophosphamide IV over 30 minutes. Treatment repeats every 21 days for 3-8 courses.|
|Drug: doxorubicin hydrochloride|Doxorubicin IV over 5 minutes. Treatment repeats every 21 days for 3-8 courses.|
|Drug: prednisone|Oral prednisone on days 1-5. Treatment repeats every 21 days for 3-8 courses.|
|Drug: vincristine sulfate|Vincristine IV over 5 minutes on day 1. Treatment repeats every 21 days for 3-8 courses.|
|Genetic: microarray analysis|genetic testing|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular risk assessment to see how well it works in predicting response to therapy in patients who are receiving treatment for non-Hodgkin's lymphoma. |  | Results from the genetic testing and PET scans at baseline and after course 3 to determine response. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I adult diffuse large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma