Pegfilgrastim and Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Aggressive B-Cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. It is not yet known whether combination chemotherapy and pegfilgrastim is more effective when given with or without rituximab in treating non-Hodgkin lymphoma. PURPOSE: This phase II trial is studying the side effects of giving pegfilgrastim and combination chemotherapy together with or without rituximab and to see how well it works in treating older patients with aggressive B-cell non-Hodgkin lymphoma.

Detailed Description
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OBJECTIVES: Determine the side effects of pegfilgrastim and cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP) with or without rituximab in older patients with aggressive B-cell non-Hodgkin lymphoma. Determine adherence to therapy regimens in these patients. Determine antitumor effectivity of immunochemotherapy. OUTLINE: This is a multicenter study. All patients receive prephase treatment comprising vincristine on day -6 and prednisone on days -6 to 0. Patients are then randomized to 1 of 2 treatment arms. Arm I (without rituximab): Patients receive pegfilgrastim subcutaneously (SC) on day 2 or 4 and CHOP comprising cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, and oral prednisone on days 1-5. Treatment repeats every 2 weeks for up to 6-8 courses in the absence of disease progression or unacceptable toxicity. Arm II (with rituximab): Patients receive pegfilgrastim and CHOP for up to 6-8 courses as in arm I. They also receive rituximab (administered 2 hours before beginning CHOP) on day 1. Treatment with rituximab repeats every 2 weeks for up to 8 courses. Patients with bulky disease or extranodal disease also undergo radiotherapy.

Official Title
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Randomized Phase II Study About the Application of Pegfilgrastim (Neulasta) at Day 2 or Day 4 Within the Treatment in Patients With Aggressive Non-Hodgkin's Lymphoma Aged 61 to 80 Years With 6 or 8 Cycles of Chemotherapy With CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) at 14-day Intervals (CHOP-14), Both With or Without the Monoclonal Anti-CD20 Antibody Rituximab

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: pegfilgrastim
* Biological: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of CD20-positive B-cell non-Hodgkin lymphoma (NHL) Confirmed by an excisional biopsy of a lymph node or by a sufficiently extensive biopsy of an extranodal involvement (if there is no lymph node involvement) Results of the immunohistological analysis of expression of the CD20 antigen by lymphoma cells must be obtained Aggressive disease, including any of the following B-cell NHL Stage III follicular lymphoma Stage III follicular lymphoma and diffuse B-cell lymphoma Lymphoblastic precursor B-cell lymphoma Diffuse large B-cell lymphoma, including any of the following subtypes: Centroblastic Immunoblastic Plasmablastic Anaplastic large cell T-cell rich B-cell lymphoma Primary effusion lymphoma Intravasal B-cell lymphoma Primary mediastinal B-cell lymphoma Mantle zone lymphoma Burkitt or Burkitt-like lymphoma Aggressive marginal zone lymphoma (monocytoid) All risk group allowed Age adjusted IPI 0-3 Previously untreated disease PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% No other serious concurrent diseases PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 61 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (without rituximab)<br>Patients receive pegfilgrastim subcutaneously (SC) on day 2 or 4 and CHOP comprising cyclophosphamide IV, doxorubicin IV, vincristine IV on day 1, and oral prednisone on days 1-5. Treatment repeats every 2 weeks for up to 6-8 courses in the absence of disease progression or unacceptable toxicity. | Biological: pegfilgrastim<br>* Given subcutaneously<br>Drug: cyclophosphamide<br>* Given IV<br>Drug: doxorubicin hydrochloride<br>* Given IV<br>Drug: prednisone<br>* Given orally<br>Drug: vincristine sulfate<br>* Given IV<br>|
| Experimental: Arm II (with rituximab)<br>Patients receive pegfilgrastim and CHOP for up to 6-8 courses as in arm I. They also receive rituximab (administered 2 hours before beginning CHOP) on day 1. Treatment with rituximab repeats every 2 weeks for up to 8 courses. | Biological: pegfilgrastim<br>* Given subcutaneously<br>Biological: rituximab<br>* Given IV<br>Drug: cyclophosphamide<br>* Given IV<br>Drug: doxorubicin hydrochloride<br>* Given IV<br>Drug: prednisone<br>* Given orally<br>Drug: vincristine sulfate<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia | median of two measurements of hemoglobin, leukocyte and platelet counts per chemotherapy cycle per Patient in correlation with median pegfilgrastim serum levels at day 1 of the next chemotherapy cycle | through chemotherapy administration (up to 112 days respectively) | 
| comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia | rates and grades of leukocytopenias and infections according to NCI-CTC criteria (version 2) | through chemotherapy administration (up to 112 days respectively) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to therapy regimens | the median overall treatment duration | through chemotherapy administration (up to 112 days respectively) | 
| Antitumor effectivity | progression-free survival | median time of observation up to 3 years | 
| Disease-free survival | period of disease-free survival | median time of observation up to 3 years | 

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