Fludeoxyglucose F 18 Positron Emission Tomography in Predicting Risk of Relapse in Patients With Non-Hodgkin's Lymphoma Who Are Undergoing Combination Chemotherapy With or Without Autologous Stem Cell or Bone Marrow Transplant

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving chemotherapy with an autologous stem cell or bone marrow transplant may allow more chemotherapy to be given so that more cancer cells are killed. Procedures, such as fludeoxyglucose F 18 positron emission tomography (FDG-PET) (done during chemotherapy) may help doctors predict a patient's risk of relapse and help plan the best treatment. PURPOSE: This phase II trial is studying how well FDG-PET works in predicting risk of relapse in patients with aggressive non-Hodgkin's lymphoma who are undergoing combination chemotherapy with or without autologous stem cell or bone marrow transplant.

Detailed Description
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OBJECTIVES: Primary Determine event-free survival of patients with aggressive non-Hodgkin's lymphoma treated with early high-dose therapy and autologous peripheral blood stem cell (PBSC) or bone marrow transplantation (BMT) based on positive fludeoxyglucose F 18 positron emission tomography (FDG-PET) results obtained during first-line chemotherapy. Compare event-free survival of patients treated with this regimen with historical event-free survival of patients with positive FDG-PET results obtained during first-line chemotherapy that are not treated with early high-dose therapy. Secondary Compare overall survival of patients treated with a standard treatment regimen vs early high-dose therapy and autologous PBSC or BMT based on FDG-PET results obtained during first-line chemotherapy. Determine the predictive value of an early negative FDG-PET result in these patients. Correlate International Prognostic Index risk category with FDG-PET results and overall outcome in these patients. OUTLINE: This is a pilot study. First-line chemotherapy: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1, oral prednisone on days 1-5, and rituximab IV on day 1 (patients with CD20-positive disease only) OR another standard first-line chemotherapy regimen. Treatment repeats every 14-21 days for 2 or 3 courses in the absence of disease progression or unacceptable toxicity. Radiographic staging: Between days 11-20 of course 2 or 3 OR days 11-13 of course 3 of first-line chemotherapy, patients receive fludeoxyglucose F 18 (FDG) IV. One hour later, patients undergo whole-body FDG-positron emission tomography (PET) and CT scan. Patients with no evidence of malignant disease by FDG-PET (i.e., negative result) receive a standard treatment regimen that may include localized radiotherapy for limited stage or bulky disease followed, 4-6 weeks later, by a repeat whole-body FDG-PET and CT scan. Patients with progressive disease after first-line chemotherapy are removed from the study. Patients with evidence of malignant disease by FDG-PET (i.e., positive result) and stable disease or better proceed to ESHAP chemotherapy. ESHAP chemotherapy: Patients receive etoposide IV over 2 hours, methylprednisolone IV, and cisplatin IV over 3 hours on days 1-4 followed by cytarabine IV over 2 hours on day 5. Patients with CD20-positive disease also receive rituximab IV on day 1. Treatment repeats every 14-21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 day after completion of course 2, patients receive filgrastim (G-CSF) subcutaneously once daily followed by leukapheresis to collect peripheral blood stem cells (PBSC). Some patients may also undergo bone marrow (BM) harvest if sufficient PBSC are not collected. Patients with a sufficient number of stem cells proceed to high-dose therapy and autologous PBSC transplantation (PBSCT) or BM transplantation (BMT). High-dose therapy and PBSCT or BMT: No more than 4 weeks after completion of PBSC collection or BM harvest, patients receive high-dose therapy that may include cyclophosphamide and total-body irradiation OR busulfan and cyclophosphamide. Patients then undergo PBSCT or BMT. Between 4-6 weeks after completion of PBSCT or BMT, patients undergo repeat whole-body FDG-PET and CT scan. Patients may also undergo consolidative radiotherapy to the sites of bulky disease at the discretion of the physician. After completion of study treatment, patients are followed at 4 weeks, every 3 months for 2 years, every 6 months for 1 year, and then annually for 2 years. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 18 months.

Official Title
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Autologous Blood or Marrow Transplantation for Aggressive Non-Hodgkin's Lymphoma Based on Early [18F] FDG-PET Scanning

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Biological: rituximab
* Drug: busulfan
* Drug: cisplatin
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: methylprednisolone
* Drug: prednisone
* Drug: vincristine sulfate
* Procedure: autologous bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation
* Procedure: positron emission tomography
* Radiation: fludeoxyglucose F 18
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes: Diffuse large B-cell lymphoma Mediastinal (thymic) B-cell lymphoma Grade 3 follicular lymphoma Anaplastic large cell lymphoma Peripheral T-cell lymphoma Must have adequate staging of disease by the following techniques: CT scan or MRI of affected sites Bone marrow biopsy (in cases where results influence the duration of chemotherapy only) Lumbar puncture (if clinically indicated) Stage I-IV disease Any International Prognostic Index risk category Radiographically measurable disease None of the following aggressive non-Hodgkin's subtypes are allowed: Mantle cell lymphoma Lymphoblastic lymphoma Burkitt's lymphoma Mycosis fungoides/Sezary's syndrome HTLV-1-associated T-cell leukemia/lymphoma Primary CNS lymphoma HIV-associated lymphoma Transformed lymphomas No prior diagnosis of another hematologic malignancy No known progressive disease during prior first-line chemotherapy No active CNS involvement by lymphoma, except CNS involvement at diagnosis that is previously treated and in remission PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-4 (0-2 for peripheral blood stem cell [PBSC] or bone marrow transplantation [BMT] patients) Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,000/mm^3* Platelet count ≥ 75,000/mm^3 NOTE: *PBSC or BMT patients only Hepatic Bilirubin ≤ 2.0 mg/dL unless due to Gilbert's disease or lymphoma* No known significant hepatic dysfunction that is not expected to improve and would preclude PBSC or BMT NOTE: *PBSC or BMT patients only Renal Creatinine ≤ 2.0 mg/dL* No known significant renal dysfunction that is not expected to improve and would preclude PBSC or BMT NOTE: *PBSC or BMT patients only Cardiovascular Ejection fraction ≥ 45% by echocardiogram or MUGA* No known significant cardiac dysfunction that is not expected to improve and would preclude PBSC or BMT NOTE: *PBSC or BMT patients only; a cardiology consult and evaluation may override ejection fraction criterion Pulmonary FEV_1 and FVC ≥ 50% of predicted for patients who have not received thoracic or mantle radiotherapy (75% of predicted for patients who have received thoracic or mantle radiotherapy)* No known significant pulmonary dysfunction that is not expected to improve and would preclude PBSC or BMT NOTE: *PBSC or BMT patients only Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 3 years except carcinoma in situ of the cervix or nonmelanoma skin cancer No known HIV positivity OR HIV negative (for PBSC or BMT patients only) No serious illness that would preclude study participation No contraindication to autologous BMT PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics No more than 3 prior courses of chemotherapy for lymphoma Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Biological: rituximab|nan|
|Drug: busulfan|nan|
|Drug: cisplatin|nan|
|Drug: cyclophosphamide|nan|
|Drug: cytarabine|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: etoposide|nan|
|Drug: methylprednisolone|nan|
|Drug: prednisone|nan|
|Drug: vincristine sulfate|nan|
|Procedure: autologous bone marrow transplantation|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Procedure: positron emission tomography|nan|
|Radiation: fludeoxyglucose F 18|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year event free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 
| Predictive value of early negative fludeoxyglucose F 18 positron emission tomography (FDG-PET) |  |  | 
| Correlation of International Prognostic Index risk category with FDG-PET results and overall outcome |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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 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, anaplastic large cell lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma