Combination Chemotherapy and Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma

Study Overview
=================
Brief Summary
-----------------
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. Combining rituximab with combination chemotherapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy in treating patients who have previously untreated non-Hodgkin's lymphoma.

Detailed Description
-----------------
OBJECTIVES: Determine the response rate, progression-free survival, and overall survival of patients with previously untreated aggressive CD20+ B-cell diffuse large cell or immunoblastic large cell lymphoma treated with rituximab, doxorubicin, etoposide, vincristine, prednisone, and cyclophosphamide. Determine the toxic effects of this regimen in these patients. Correlate tumor proliferation rate (MIB-1), bcl-2 expression, and p53 overexpression with complete response rate, progression-free survival, and overall survival in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive rituximab IV on day 1; doxorubicin IV continuously, etoposide IV continuously, and vincristine IV continuously on days 1-4; oral prednisone twice daily on days 1-5; and cyclophosphamide IV on day 5. Patients also receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients with complete or partial response receive 2 additional courses. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 1 year.

Official Title
-----------------
Phase II Study Of Dose-Adjusted Epoch-Rituximab (EPOCH-R) Chemotherapy For Patients With Previously Untreated Aggressive CD20+ B-Cell Non-Hodgkin's Lymphoma (NHL)

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Biological: filgrastim
* Biological: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: prednisone
* Drug: vincristine sulfate


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed stage II, III, or IV diffuse large cell lymphoma and WHO variants CD20+ large B-cell lymphoma, including those with immunoblastic features CD20+ thymic B-cell lymphoma No evidence of indolent lymphoma No mantle cell lymphomas or equivocal B-cell lymphomas that express markers of mantle cell lymphoma (e.g., cyclin D) or other subtypes No known lymphomatous involvement of the CNS, including the parenchyma or leptomeninges PATIENT CHARACTERISTICS: Age: Not specified Performance status: CALGB 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,000/mm3* Platelet count at least 100,000/mm3* NOTE: * Unless due to lymphoma Hepatic: Bilirubin no greater than 2.0 mg/dL* NOTE: * Unless due to lymphoma or Gilbert's disease Renal: Creatinine no greater than 1.5 mg/dL* NOTE: * Unless due to lymphoma Cardiovascular: LVEF greater than 45% No ischemic heart disease No myocardial infarction or congestive heart failure within the past year Other: HIV negative Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior cytotoxic chemotherapy No other concurrent chemotherapy Endocrine therapy: Prior short-course of glucocorticoids allowed No concurrent hormones except for non-disease-related conditions (e.g., insulin for diabetes) No concurrent steroids except for adrenal failure No concurrent dexamethasone or other steroidal antiemetics Radiotherapy: Prior limited-field radiotherapy allowed Surgery: Not specified
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPOCH-Rituximab<br>Addition of monoclonal antibody therapy to chemotherapy for treatment of pts with aggressive CD20+ NHL | Biological: filgrastim<br>* Cycle 1: 300 ug (BW < = 70 kg) or 480ug (BW >70 kg) sub Q injection Day 6 until ANC > 5000/uL after nadir counts Subsequent cycle dosages based on previous cycle toxicity or Day 1 Tx toxicity<br>* Other names: G-CSF;Biological: rituximab<br>* 375 mg/sq m IV infusion Day 1 Cycle 1 Subsequent cycle dosage based on previous cycle or day 1 of tx toxicities<br>Drug: cyclophosphamide<br>* 750 mg/sq m IV infusion on Day 5 Cycle 1 Subsequent cycle dosage based on previous cycle or day 1 treatment toxicities<br>Drug: doxorubicin hydrochloride<br>* 10 mg/sq m/day continuous IV infusion on Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and Day 1 treatment toxicities<br>Drug: etoposide<br>* 50 mg/sq m/day continuous IV infusion Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and day 1 of treatment toxicities<br>Drug: prednisone<br>* 60 mg/sq m PO bid days 1-5 of ea cycle<br>Drug: vincristine sulfate<br>* 0.4 mg/sq m/day continuous IV infusion uncapped on Days 1-4 Cycle 1 Subsequent cycle dosages based on previous cycle and day 1 of treatment toxicities<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response |  | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free Survival |  | Study entry to progression or tx related death | 
| Overall survival |  | Study entry to death from any cause | 
| Toxicity |  | q 2cycles on Tx, then q 6 mon for 2 yrs, then at relapse | 

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