Completed

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

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What is being tested

Etoposide

+ Rituximab
+ Prednisone
Drug
Biological
Diagnostic Test
Procedure
Other
Who is being recruted

Diffuse Large B-Cell Lymphoma (DLBCL)
+2

+ Primary Mediastinal Large B-cell Lymphoma
+ Burkitt Lymphoma
Over 12 Years

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: May 1993

See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: June 22, 2025
Sourced from a government-validated database.Claim as a partner
Study start date: May 8, 1993Actual date on which the first participant was enrolled.

5-Drug Combination Chemotherapy with Hematologic Toxicity Attenuation. Etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin)(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), Granulocyte colony-stimulating factor (G-CSF), NSC-614629. 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 etoposide phosphate, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin)(EPOCH) infusional chemotherapy given intensively with granulocyte colony-stimulating factor (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 aggressive 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. Human immunodeficiency virus (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 cluster of differentiation 20 (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 TitleDose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Adults and Children With Previously Untreated Patients With Aggressive Non-Hodgkin's Lymphoma 
Principal SponsorNational Cancer Institute (NCI)
Last updated: June 22, 2025
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
348 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are assigned to groups based on specific criteria, such as their medical history or a doctor's recommendation. This approach ensures that treatments are given to those who may benefit the most, based on known factors.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 12 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Diffuse Large B-Cell Lymphoma (DLBCL)
Primary Mediastinal Large B-cell Lymphoma
Burkitt Lymphoma
Anaplastic Large-Cell Lymphoma
Gray Zone Lymphoma
Criteria

* 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, National Cancer Institute (NCI). Tissue blocks from patients treated in extramural sites must be forwarded to the NCI for analysis of B-cell leukemia/lymphoma 2 (bcl-2) by immunohistochemistry (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 mediastinal gray zone lymphoma (MGZL) and primary mediastinal B-cell lymphoma (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). Human immunodeficiency virus (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 creatinine (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; absolute neutrophil count (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 multi-gated acquisition (MUGA) is obtained, the left ventricular ejection fraction (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.

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Subgroup 1 (SG1) - All participants who received combination Rituximab (EPOCH-R). Rituximab 375 mg/m\^2 intravenous (IV) on day 1, every 21 days, prednisone 100mg by mouth (PO) twice a day (bid) on days 1 through 5 every 21 days, and cyclophosphamide 750mg/m\^2 on day 5 every 21 days. Doxorubicin 10mg/m\^2/day, vincristine 0.4mg/m\^2/day, and etoposide 50mg/m\^2/day were delivered as continuous intravenous (CIV) infusions over 96 hours starting on day 1 every 21 days. Dose levels were adjusted on doxorubicin, etoposide, and cyclophosphamide each cycle based on neutrophil nadir.
Group II
Experimental
Subgroup 2 (SG2) - EPOCH alone: All participants who received Prednisone 100mg by mouth (PO) twice a day (bid) on days 1 through 5 every 21 days, and cyclophosphamide 750mg/m\^2 on day 5 every 21 days. Doxorubicin 10mg/m\^2/day, vincristine 0.4mg/m\^2/day, and etoposide 50mg/m\^2/day were delivered as continuous intravenous (CIV) infusions over 96 hours starting on day 1 every 21 days. Dose levels were adjusted on doxorubicin, etoposide, and cyclophosphamide each cycle based on neutrophil nadir.
Study Objectives
Primary Objectives

Overall response defined as a Complete Response + Partial Response was measured by the Response Criteria. Complete Response is disappearance of all signs and symptoms of lymphoma for a period of at least one month. Partial Response is 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting for a period of at least one month.

The Dixon-Simon method will be used to determine whether large B-cell lymphomas expressing BCL-2 (+) participants may experience an improved progression free survival with Etoposide, VP-16, and Doxorubicin with Prednisone, Cyclophosphamide, and Rituximab (EPOCH-R) compared to EPOCH alone, and to obtain a concurrent, precisely determined measure of progression free survival. PFS is the time from start of treatment to documented evidence of disease progression. Progression is an increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions, or the appearance of any new lesions measured by the Response Criteria.
Secondary Objectives

Here is the proportion of participants with adverse events leading to discontinuation of therapy. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the participant and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 5 locations
Suspended
Holy Cross Hospital, Fort LauderdaleFort Lauderdale, United StatesSee the location
Suspended
University of Maryland, BaltimoreBaltimore, United States
Suspended
National Institutes of Health Clinical CenterBethesda, United States
Suspended
Brigham and Women's HospitalBoston, United States
Completed5 Study Centers