Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without rituximab in treating aggressive non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying how well giving cyclophosphamide, doxorubicin, vincristine, and prednisone together with or without rituximab works in treating older patients who have aggressive non-Hodgkin's lymphoma. (This trial is no longer randomized as of 6/2005).

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with vs without rituximab in elderly patients with aggressive non-Hodgkin's lymphoma. Compare the efficacy of 6 vs 8 courses of CHOP chemotherapy in patients treated with these regimens. Compare the rate of complete remission, rate of primary progression, tumor control, disease-free survival, overall survival, and relapse after radiotherapy in patients treated with these regimens. Compare the safety and side effects of these regimens in these patients. Secondary Compare short-term and long-term side effects of these regimens in these patients. Compare quality of life of patients treated with these regimens. Compare the cost of these regimens in these patients. Determine relapse in patients treated with these regimens who received involved-field radiotherapy. OUTLINE: This is a randomized (randomized part of study completed as of 6/2005), open-label, multicenter study. Patients are stratified according to participating center, value for serum lactic dehydrogenase (no greater than upper limit of normal [ULN] vs greater than ULN), bulky disease present (no vs yes), stage (I or II vs III or IV), general ECOG status of patient (0 or 1 vs 2), and age (61 to 70 vs 71-80). Patients are randomized to 1 of 4 treatment arms. Patients with CD20-negative lymphoma are randomized to arms I or II only. Prephase treatment:Patients receive vincristine IV on day -6 and prednisone on day -6 to day 0 before initiating CHOP chemotherapy. Arm I (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-12 of each CHOP course. Treatment repeats every 2 weeks for 6 courses. Arm II (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm I for a total of 8 courses. Arm III: Patients receive standard CHOP chemotherapy and G-CSF as in arm I. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses. Arm IV (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm II. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses. In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of the last chemotherapy course, after complete recovery of bone marrow, and after complete remision of mucositis, patients with sites of initial bulky disease or extranodal involvement undergo radiotherapy 5 times a week for 4 weeks. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 1580 patients will be accrued for this study within 5 years.

Official Title
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Randomised Study Comparing 6 And 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 In Patients Aged 61 To 80 Years With Aggressive Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Biological: rituximab
* Drug: CHOP regimen
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) by an excisional biopsy of a lymph node or an extensive biopsy of an extranodal involvement (if there is no lymph node involvement) CD20^+ B-cell lymphoma or CD20^- B-cell and T-cell lymphoma allowed B-cell NHL including the following: Stage III follicular lymphoma Stage III follicular lymphoma and diffuse B-cell lymphoma Lymphoblastic precursor B-cell lymphoma Diffuse large cell B-cell lymphoma 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, blastoid Burkitt's lymphoma Burkitt-like lymphoma Aggressive marginal zone lymphoma (monocytoid) T-cell NHL including the following: Lymphoblastic precursor T-cell lymphoma Peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS) Lennert's lymphoma T-zone lymphoma T-cell lymphoma of the angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) type Anaplastic large cell lymphoma ALK^+ ALK^- Extranodal NK/T-cell lymphoma, nasal type Intestinal T/NK-cell lymphoma (with or without enteropathy) Hepatosplenic gamma-delta lymphoma Subcutaneous panniculitis-like PTCL Aggressive T/NK PTCL Anaplastic large-cell NHL, NOS Bone marrow involvement no more than 25% No lymphoma that is clearly restricted to the CNS or originating from the gastrointestinal tract PATIENT CHARACTERISTICS: Age 61 to 80 Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy Not specified Hematopoietic WBC at least 2,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 2 times upper limit of normal (ULN) No active hepatitis infection Renal Creatinine no greater than 2 times ULN Cardiovascular No Canadian Cardiovascular Society class III or IV angina pectoris No New York Heart Association class III or IV cardiac failure Ejection fraction at least 50% Fractional shortenings at least 25% by echocardiography or nuclear medicine examination Pulmonary FEV1 at least 50% Diffusion capacity at least 50% Other No uncontrolled diabetes mellitus No known hypersensitivity to any study medications No other concurrent malignancy HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery Not specified Other Must not have already initiated lymphoma therapy (except for the prephase treatment specified for this study) No other concurrent lymphoma therapy No concurrent participation in another treatment study

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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S6<br>6x CHOP-14 | Biological: filgrastim<br> <br> Drug: CHOP regimen<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: prednisone<br> <br> Drug: vincristine sulfate<br> <br> Radiation: radiation therapy<br>* 36Gy on BULK and extranodal involvement<br>|
| Experimental: R6<br>6x CHOP-14 + 8x Rituximab | Biological: filgrastim<br> <br> Biological: rituximab<br> <br> Drug: CHOP regimen<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: prednisone<br> <br> Drug: vincristine sulfate<br> <br> Radiation: radiation therapy<br>* 36Gy on BULK and extranodal involvement<br>|
| Experimental: S8<br>8x CHOP-14 | Biological: filgrastim<br> <br> Drug: CHOP regimen<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: prednisone<br> <br> Drug: vincristine sulfate<br> <br> Radiation: radiation therapy<br>* 36Gy on BULK and extranodal involvement<br>|
| Experimental: R8<br>8x CHOP-14 + 8x Rituximab | Biological: filgrastim<br> <br> Biological: rituximab<br> <br> Drug: CHOP regimen<br> <br> Drug: cyclophosphamide<br> <br> Drug: doxorubicin hydrochloride<br> <br> Drug: prednisone<br> <br> Drug: vincristine sulfate<br> <br> Radiation: radiation therapy<br>* 36Gy on BULK and extranodal involvement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure at 3 years within the study and then periodically after study completion |  | 3 years within the study and then periodically after study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate at 3 years within the study and then periodically after study completion |  | 3 years within the study and then periodically after | 
| Progression rate |  | 3 years within the study and then periodically after | 
| Survival |  | 3 years within the study and then periodically after | 
| Tumor control |  | 3 years within the study and then periodically after | 
| Disease-free survival |  | 3 years within the study and then periodically after | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, stage III grade 1 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III grade 2 follicular 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, contiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, stage I adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic 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, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, stage I marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma