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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00001337
Recruitment Status : Active, not recruiting
First Posted : November 4, 1999
Last Update Posted : April 25, 2023
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma (DLBCL) Primary Mediastinal Large B-cell Lymphoma Burkitt Lymphoma Anaplastic Large-Cell Lymphoma Gray Zone Lymphoma Drug: EPOCH Biological: Rituximab Phase 2

Detailed Description:


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.



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.


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.


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 348 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Adults and Children With Previously Untreated Patients With Aggressive Non-Hodgkin's Lymphoma
Actual Study Start Date : May 8, 1993
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2025

Arm Intervention/treatment
Experimental: Arm A
EPOCH + Rituximab every 3 weeks for 6 cycles.
Combination chemotherapy given with Rituximab (EPOCH-R) IV every 3 weeks for 6 cycles.

Biological: Rituximab
Rituximab given on Day 1 of combination chemotherapy (EPOCH-R) every 3 weeks for 6 cycles.

Primary Outcome Measures :
  1. Overall response and PFS [ Time Frame: Time of progression ]
    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.

Secondary Outcome Measures :
  1. Safety and Toxicity [ Time Frame: Initiation of study drug until 30 days after treatment ]
    the proportion of patients with adverse events leading to discontinuation of therapy

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Non-Hodgkin's lymphomas in the following categories: mediastinal gray zone lymphoma and primary mediastinal B cell


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001337

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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Mark J Roschewski, M.D. National Cancer Institute (NCI)
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00001337    
Obsolete Identifiers: NCT00018980
Other Study ID Numbers: 930133
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: April 25, 2023
Last Verified: March 7, 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Primary Mediastinal B-Cell Lymphoma
CD20 +
Diffuse Large B-Cell Lymphoma
Anaplastic Large Cell Lymphoma
De Novo
Additional relevant MeSH terms:
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Burkitt Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, T-Cell
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents