Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin's Lymphoma
2 other identifiers
interventional
348
1 country
5
Brief 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, CTX, NSC-26271; Doxorubicin, DOX, NSC-123127; with Granulocyte Colony-Stimulating Factor (Amgen), Granulocyte colony-stimulating factor (G-CSF), NSC-614629.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 1993
Longer than P75 for phase_2
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 8, 1993
CompletedFirst Submitted
Initial submission to the registry
November 3, 1999
CompletedFirst Posted
Study publicly available on registry
November 4, 1999
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 24, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
May 24, 2024
CompletedResults Posted
Study results publicly available
June 12, 2025
CompletedJune 22, 2025
June 1, 2025
31.1 years
November 3, 1999
April 15, 2025
June 12, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
Time frame was from beginning of therapy until the end of therapy, an average of 6 months
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.
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)
Proportion of Participants With Serious and/or Non-serious Adverse Events Leading to Discontinuation of Therapy
Initiation of study drug until 30 days after treatment, an average of 6 months
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Time frame is from study entry until 30 days after completing study therapy, approximately 5 years.
Study Arms (2)
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.
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.
Interventions
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.
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.
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.
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.
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.
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.
Baseline and/or on completion of therapy.
Baseline and/or on completion of therapy.
Baseline and/or on completion of therapy.
As clinically indicated.
As clinically indicated.
Nausea and/or vomiting.
Nausea and/or vomiting.
Gastroesophageal reflux disease (GERD).
Constipation.
Constipation
Eligibility Criteria
You may qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Holy Cross Hospital, Fort Lauderdale
Fort Lauderdale, Florida, 33308, United States
University of Maryland, Baltimore
Baltimore, Maryland, 21201-1595, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
St. Luke's Roosevelt Hospital
New York, New York, 10025, United States
Related Publications (10)
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.
PMID: 2580468BACKGROUNDLai 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.
PMID: 1682280BACKGROUNDDeVita 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.
PMID: 46388BACKGROUNDLai 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.
PMID: 35882475DERIVEDMiljkovic 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.
PMID: 34432874DERIVEDKurtz 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.
PMID: 30125215DERIVEDMelani 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.
PMID: 29748435DERIVEDWilson 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.
PMID: 25024303DERIVEDDunleavy 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.
PMID: 24224624DERIVEDDunleavy 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.
PMID: 23574119DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Mark J. Roschewski
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Mark J Roschewski, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Investigator
Study Record Dates
First Submitted
November 3, 1999
First Posted
November 4, 1999
Study Start
May 8, 1993
Primary Completion
May 24, 2024
Study Completion
May 24, 2024
Last Updated
June 22, 2025
Results First Posted
June 12, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.