Positron Emission Tomography Using Fludeoxyglucose F 18 in Predicting Response to Treatment in Patients Who Are Receiving Rituximab and Combination Chemotherapy for Newly Diagnosed Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Diagnostic procedures, such as positron emission tomography (PET) using fludeoxyglucose F 18, may help in learning how well chemotherapy works to kill cancer cells and allow doctors to plan better treatment. Comparing results of diagnostic procedures done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment. PURPOSE: This clinical trial is studying positron emission tomography using fludeoxyglucose F 18 to see how well it works in predicting response to treatment in patients who are receiving rituximab and combination chemotherapy for newly diagnosed non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the positive and negative predictive values of early positron emission tomography (PET) scanning using fludeoxyglucose F 18 in terms of the probability of patients with newly diagnosed intermediate- or high-grade non-Hodgkin's lymphoma who achieve or do not achieve complete remission, after treatment with 1 course of rituximab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone. Determine event free and overall survival of patients with an early positive and negative PET scan treated with this regimen. Determine the predictive value of early PET scan response ratio as a continuous variable in terms of response to therapy (assessed at the end of therapy), disease-free survival, and overall survival, in patients treated with this regimen. Correlate International Prognostic Index score at presentation with early PET scan results and overall outcome in patients treated with this regimen. Correlate the degree of neutropenia 7 to 10 days after the first course of treatment with rituximab and combination chemotherapy with PET scan response and pre-treatment blood CD34-positive cell concentration in these patients. OUTLINE: This is a multicenter study. Patients receive fludeoxyglucose F 18 (^18FDG) IV. Beginning 1 hour later, patients undergo whole-body positron emission tomography (PET) scanning. Patients also undergo conventional radiographic staging of their disease. Patients then receive standard R-CHOP (or an alternative regimen) comprising 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 once daily on days 1-5. Treatment repeats every 14-21 days for up to 4 courses in the absence of unacceptable toxicity. Patients undergo repeat ^18FDG-PET scanning between days 7-10 of course 1, between courses 3 and 4, and then at the completion of R-CHOP. Patients also undergo radiographic restaging of their disease between courses 3 and 4 and at the completion of R-CHOP. After completion of study treatment, patients are followed every 3-4 months for 2 years, every 6 months for 1 year, and then annually for 3 years. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 2 years.

Official Title
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Prognostic Significance of Early Positron Emission Tomography (PET) With Fluorine-18 Fluorodeoxyglucose ([18F] FDG) in Intermediate and High Grade 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
* Procedure: positron emission tomography
* Radiation: fludeoxyglucose F 18


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed newly diagnosed non-Hodgkin's lymphoma (NHL) Intermediate- or high-grade disease Stage I-IV disease Any of the following subtypes are allowed: Diffuse large B-cell lymphoma Anaplastic large cell lymphoma Mantle cell lymphoma Grade 3 follicular lymphoma Mediastinal B-cell lymphoma The following subtypes are not allowed: Lymphoblastic lymphoma Mycosis fungoides/Sézary's syndrome HTLV-1 associated T-cell leukemia or lymphoma Primary CNS lymphoma HIV-associated lymphoma Transformed lymphoma Burkitt's lymphoma Adequate staging of lymphoma by any of the following methods: CT scan or MRI of affected sites Unilateral or bilateral bone marrow biopsy Positive pre-treatment positron emission tomography (PET) scan Lumbar puncture Radiographically measurable disease by PET scan Any International Prognostic Index risk category allowed No prior diagnosis of another hematologic malignancy NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,000/mm^3* Platelet count ≥ 75,000/mm^3* NOTE: *Unless due to NHL Hepatic Bilirubin ≤ 2.0 mg/dL* (excluding Gilbert's disease) NOTE: *Unless due to NHL Renal Creatinine ≤ 2.0 mg/dL (unless due to NHL) Cardiovascular Ejection fraction ≥ 45% by echocardiogram or MUGA Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No other malignancy within the past 5 years except superficial nonmelanoma skin cancer or carcinoma in situ of the cervix No other serious co-morbid disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No prior rituximab for NHL No concurrent filgrastim [G-CSF] during course 1 of study treatment except for patients > 70 years of age OR patients with active infection Chemotherapy No prior chemotherapy for NHL Endocrine therapy No prior steroids for NHL Radiotherapy No prior radiotherapy for NHL Concurrent consolidation radiotherapy to sites of bulky disease allowed at the discretion of the attending physician Surgery Not specified Other No other prior treatment for NHL

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: Diagnostic
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 14-21 days for up to 4 courses in the absence of unacceptable toxicity.|
|Drug: cyclophosphamide|Cyclophosphamide IV over 30 minutes. Treatment repeats every 14-21 days for up to 4 courses in the absence of unacceptable toxicity.|
|Drug: doxorubicin hydrochloride|Doxorubicin IV over 5 minutes. Treatment repeats every 14-21 days for up to 4 courses in the absence of unacceptable toxicity.|
|Drug: prednisone|Oral prednisone once daily on days 1-5. Treatment repeats every 14-21 days for up to 4 courses in the absence of unacceptable toxicity.|
|Drug: vincristine sulfate|Vincristine IV over 5 minutes on day 1. Treatment repeats every 14-21 days for up to 4 courses in the absence of unacceptable toxicity.|
|Procedure: positron emission tomography|Beginning 1 hour after receiving fludeoxyglucose F 18, patients undergo whole-body positron emission tomography (PET) scanning. Patients undergo repeat ^18FDG-PET scanning between days 7-10 of course 1, between courses 3 and 4, and then at the completion of R-CHOP.|
|Radiation: fludeoxyglucose F 18|Patients receive fludeoxyglucose F 18 (^18FDG) IV.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission as measured by positron emission tomography (PET) at 7-10 days after R-CHOP, and after completion of study treatment |  | at 7-10 days after R-CHOP, and after completion of study treatment | 
| Overall survival at 7-10 days after R-CHOP, and after completion of study treatment |  | at 7-10 days after R-CHOP, and after completion of study treatment | 
| Disease-free survival at 7-10 days after R-CHOP, and after completion of study treatment |  | at 7-10 days after R-CHOP, and after completion of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage I adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, anaplastic large cell lymphoma