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Diffuse Large B-Cell Lymphoma (DLBCL)Phase 2NCT00001337

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

A Phase 2 study testing Etoposide, Rituximab and Prednisone in people with Diffuse Large B-Cell Lymphoma (DLBCL) and Primary Mediastinal Large B-cell Lymphoma, run by National Cancer Institute (NCI) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Etoposide, Rituximab and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
348 participants
Where
5 sitesUnited States
Study dates
8 May 1993to 24 May 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

None listed.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Maryland, Baltimore

    Baltimore, Maryland, 21201-1595

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Holy Cross Hospital, Fort Lauderdale

    Fort Lauderdale, Florida, 33308

  • St. Luke's Roosevelt Hospital

    New York, New York, 10025

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Keywords
Primary Mediastinal B-Cell Lymphoma, CD20 +, Diffuse Large B-Cell Lymphoma, Anaplastic Large Cell Lymphoma, De Novo
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Burkitt Lymphoma, Lymphoma, Large-Cell, Anaplastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EtoposideDrug

    Also called VP-16

    Etoposide 50mg/m^2/day were delivered as continuous intravenous (CIV) infusions over 96 hours starting on day 1 every 21 days.

    Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.

  • RituximabBiological

    Also called Rituxan

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

    Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.

  • PrednisoneDrug

    Also called Rayos, Deltasone, Prednisone Intensol

    Prednisone 100mg by mouth (PO) twice a day (bid) on days 1 through 5 every 21 days.

    Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.

  • CyclophosphamideDrug

    Also called Cytoxan

    Cyclophosphamide 750mg/m^2 on day 5 every 21 days.

    Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.

  • VincristineDrug

    Also called Marqibo, Vincasar PFS

    Vincristine 0.4mg/m^2/day.

    Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.

  • DoxorubicinDrug

    Also called Lipodox, Lipodox 50, Doxil

    Doxorubicin 10mg/m^2/day.

    Combination chemotherapy given with Rituximab, Etoposide, VP-16; Prednisone, Cyclophosphamide, Vincristine, and Doxorubicin (EPOCH-R) intravenous (IV) every 3 weeks for 6 cycles.

  • MRIDiagnostic test

    Also called Magnetic resonance imaging

    Baseline and/or on completion of therapy.

  • CTDiagnostic test

    Also called Computed tomography

    Baseline and/or on completion of therapy.

  • BiopsyProcedure or surgery

    Baseline and/or on completion of therapy.

  • PET scanDiagnostic test

    Also called positron emission tomography scan

    As clinically indicated.

  • LaparotomyProcedure or surgery

    As clinically indicated.

  • OndansetronOther

    Also called Zofran ODT, Zuplenz, Zofran

    Nausea and/or vomiting.

  • ProchlorperazineOther

    Also called Compro

    Nausea and/or vomiting.

  • OmeprazoleOther

    Also called Prilosec OTC, Zegerid, OmePPi

    Gastroesophageal reflux disease (GERD).

  • Docusate Sodium + SennosidesOther

    Also called Senna-Plus, Colace 2-in-1, Dok Plus

    Constipation.

  • LactuloseOther

    Also called Kristalose, Enulose, Generlac

    Constipation

Study groups in NCT00001337
Study groupRoleWhat they receive
With EPOCH-R (Etoposide, Doxorubicin, Prednisone, Cyclophosphamide and Rituximab)ExperimentalSubgroup 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.
Receives: Drug: Etoposide; Biological: Rituximab; Drug: Prednisone; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Diagnostic Test: MRI; Diagnostic Test: CT; Procedure: Biopsy; Diagnostic Test: PET scan; Procedure: Laparotomy; Other: Ondansetron; Other: Prochlorperazine; Other: Omeprazole; Other: Docusate Sodium + Sennosides; Other: Lactulose
EPOCH Alone (Etoposide, Doxorubicin, Prednisone, and Cyclophosphamide)ExperimentalSubgroup 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.
Receives: Drug: Etoposide; Drug: Prednisone; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Diagnostic Test: MRI; Diagnostic Test: CT; Procedure: Biopsy; Diagnostic Test: PET scan; Procedure: Laparotomy; Other: Ondansetron; Other: Prochlorperazine; Other: Omeprazole; Other: Docusate Sodium + Sennosides; Other: Lactulose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response (Complete Response + Partial Response)

    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.

    Measured: Time frame was from beginning of therapy until the end of therapy, an average of 6 months

  2. Progression Free Survival (PFS)

    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.

    Measured: Progression free survival was calculated from study entry until progression or death from any cause. Median follow up of evaluable participants was 5 years (range 2-7 years)

Secondary outcomes (1)

  1. Proportion of Participants With Serious and/or Non-serious Adverse Events Leading to Discontinuation of Therapy

    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.

    Measured: Initiation of study drug until 30 days after treatment, an average of 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 1999 (estimated)
  2. Study start8 May 1993
  3. Primary completion24 May 2024
  4. Study completion24 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
348 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001337
Sponsor's protocol ID
930133
Other IDs
93-C-0133
Status last verified
Jun 2025
First submitted
3 Nov 1999
Last updated
22 Jun 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Publications

  • Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596-602. doi: 10.7326/0003-4819-102-5-596.

    PubMed 2580468

  • Lai GM, Chen YN, Mickley LA, Fojo AT, Bates SE. P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines. Int J Cancer. 1991 Nov 11;49(5):696-703. doi: 10.1002/ijc.2910490512.

    PubMed 1682280

  • DeVita VT Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248-50. doi: 10.1016/s0140-6736(75)91142-3.

    PubMed 46388

  • Lai C, Cole DE, Steinberg SM, Lucas N, Dombi E, Melani C, Roschewski M, Balis F, Widemann BC, Wilson WH. Doxorubicin pharmacokinetics and toxicity in patients with aggressive lymphoma and hepatic impairment. Blood Adv. 2023 Feb 28;7(4):529-532. doi: 10.1182/bloodadvances.2022007431.

    PubMed 35882475

  • Miljkovic MD, Melani C, Pittaluga S, Lakhotia R, Lucas N, Jacob A, Yusko E, Jaffe ES, Wilson WH, Roschewski M. Next-generation sequencing-based monitoring of circulating tumor DNA reveals clonotypic heterogeneity in untreated PTCL. Blood Adv. 2021 Oct 26;5(20):4198-4210. doi: 10.1182/bloodadvances.2020003679.

    PubMed 34432874

  • Kurtz DM, Scherer F, Jin MC, Soo J, Craig AFM, Esfahani MS, Chabon JJ, Stehr H, Liu CL, Tibshirani R, Maeda LS, Gupta NK, Khodadoust MS, Advani RH, Levy R, Newman AM, Duhrsen U, Huttmann A, Meignan M, Casasnovas RO, Westin JR, Roschewski M, Wilson WH, Gaidano G, Rossi D, Diehn M, Alizadeh AA. Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2018 Oct 1;36(28):2845-2853. doi: 10.1200/JCO.2018.78.5246. Epub 2018 Aug 20.

    PubMed 30125215

  • Melani C, Advani R, Roschewski M, Walters KM, Chen CC, Baratto L, Ahlman MA, Miljkovic MD, Steinberg SM, Lam J, Shovlin M, Dunleavy K, Pittaluga S, Jaffe ES, Wilson WH. End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making. Haematologica. 2018 Aug;103(8):1337-1344. doi: 10.3324/haematol.2018.192492. Epub 2018 May 10.

    PubMed 29748435

  • Wilson WH, Pittaluga S, Nicolae A, Camphausen K, Shovlin M, Steinberg SM, Roschewski M, Staudt LM, Jaffe ES, Dunleavy K. A prospective study of mediastinal gray-zone lymphoma. Blood. 2014 Sep 4;124(10):1563-9. doi: 10.1182/blood-2014-03-564906. Epub 2014 Jul 14.

    PubMed 25024303

  • Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. doi: 10.1056/NEJMoa1308392.

    PubMed 24224624

  • Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. doi: 10.1056/NEJMoa1214561.

    PubMed 23574119

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Etoposide, Rituximab and Prednisone in people with Diffuse Large B-Cell Lymphoma (DLBCL) and Primary Mediastinal Large B-cell Lymphoma, run by National Cancer Institute (NCI) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response (Complete Response + Partial Response) (time frame: Time frame was from beginning of therapy until the end of therapy, an average of 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00001337, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.

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