Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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5-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation. EPOCH: Etoposide, VP-16, NSC-141540; Prednisone, PRED, NSC-10023; Vincristine, VCR, NSC-67574; Cyclophosphamide, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; with Granulocyte Colony-Stimulating Factor (Amgen), G-CSF, NSC-614629.

Detailed Description
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Background: The treatment of the intermediate and aggressive non-Hodgkin's lymphomas in adults and children commonly induces complete responses in a sizable fraction of the treated population, and about 2/3 of the complete responders appear to have prolonged disease-free survival. The present study assesses the activity and tolerability in previously untreated patients of a regimen of EPOCH infusional chemotherapy given intensively with G-CSF support. Objectives: Primary: Assess complete response (CR) and progression-free survival (PFS) of dose-adjusted EPOCH-Rituximab (DA-EPOCH-R) with G-CSF in agressive B-cell lymphomas. Eligibility: Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma (MGZL) and primary mediastinal B cell lymphoma (PMBL). Patients greater than or equal to 12 years old. Any Stage for PMBL and MGZL. No prior systemic chemotherapy. HIV negative. Design: This study will estimate the complete response rate of a group of previously untreated patients and the extent to which EPOCH infusional drug delivery accompanied by a hematopoietic growth factor can increase the dose intensity of treatment. Patients receive prednisone orally for 5 days, a 96 hour infusion of vincristine, doxorubicin, and etoposide, and a bolus of cyclophosphamide on day 5. Cycles are repeated every 21 days for a total of 6-8 cycles. Patients with CD20 expressing tumors (i.e. mature B-cell lymphomas) will also receive rituximab, the humanized monoclonal antibody against the CD20 receptor on day 1 of each cycle. A total of 348 patients will be enrolled on this protocol.

Official Title
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Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Adults and Children With Previously Untreated Patients With Aggressive Non-Hodgkin's Lymphoma

Conditions
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Diffuse Large B-Cell Lymphoma (DLBCL), Primary Mediastinal Large B-cell Lymphoma, Burkitt Lymphoma, Anaplastic Large-Cell Lymphoma, Gray Zone Lymphoma

Intervention / Treatment
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* Drug: EPOCH
* Biological: Rituximab


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma and primary mediastinal B cell lymphoma. Diagnosis confirmed by staff of the Hematopathology Section, Laboratory of Pathology, NCI. Tissue blocks from patients treated in extramural sites must be forwarded to the NCI for analysis of bcl-2 by IHC and other markers within 1 month of study entry. Patients greater than or equal to 12 years old. Stage and Prognosis of Patients: Any stage for MGZL and PMBL. No prior systemic chemotherapy. Patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids and/or cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome). HIV negative. Not pregnant or nursing. Adequate major organ function [in adults: serum creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 60 ml/min; and in children serum CR less than or equal to age-adjusted normal (age 12 to 15 maximum serum creatinine 1.2 mg/dl and age greater than 15 maximum serum creatinine 1.5 mg/dl); bilirubin less than 1.5 mg/dl; ANC greater than 1,000 and platelets greater than 100,000) unless impairment is due to organ involvement by lymphoma or immune-mediated mechanism caused by lymphoma. No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If MUGA is obtained, the LVEF should exceed 40%. No other serious concomitant medical illnesses or uncontrolled active infection that would jeopardize the patient's ability to receive the regimen with reasonable safety. No history of unrelated (non-lymphomatous) neoplasms within past 5 years other than non-melanoma skin cancer or in-situ cancer. Ability to give informed consent.

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>EPOCH + Rituximab every 3 weeks for 6 cycles. | Drug: EPOCH<br>* Combination chemotherapy given with Rituximab (EPOCH-R) IV every 3 weeks for 6 cycles.<br>Biological: Rituximab<br>* Rituximab given on Day 1 of combination chemotherapy (EPOCH-R) every 3 weeks for 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response and PFS | The Dixon-Simon method will be used to determine whether large B-cell lymphomas expressing BCL-2 (+) patients may experience an improved progression free survival with EPOCH-R compared to EPOCH alone, and to obtain a concurrent, precisely determined measure of progression free survival. | Time of progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Toxicity | the proportion of patients with adverse events leading to discontinuation of therapy | Initiation of study drug until 30 days after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Mediastinal B-Cell Lymphoma, CD20 +, Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, De Novo