Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin's Lymphoma
NCT ID: NCT00001337
Last Updated: 2025-06-22
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
348 participants
INTERVENTIONAL
1993-05-08
2024-05-24
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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With EPOCH-R (Etoposide, Doxorubicin, Prednisone, Cyclophosphamide and Rituximab)
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.
Etoposide
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
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
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
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
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
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.
MRI
Baseline and/or on completion of therapy.
CT
Baseline and/or on completion of therapy.
Biopsy
Baseline and/or on completion of therapy.
PET scan
As clinically indicated.
Laparotomy
As clinically indicated.
Ondansetron
Nausea and/or vomiting.
Prochlorperazine
Nausea and/or vomiting.
Omeprazole
Gastroesophageal reflux disease (GERD).
Docusate Sodium + Sennosides
Constipation.
Lactulose
Constipation
EPOCH Alone (Etoposide, Doxorubicin, Prednisone, and Cyclophosphamide)
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.
Etoposide
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.
Prednisone
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
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
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
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.
MRI
Baseline and/or on completion of therapy.
CT
Baseline and/or on completion of therapy.
Biopsy
Baseline and/or on completion of therapy.
PET scan
As clinically indicated.
Laparotomy
As clinically indicated.
Ondansetron
Nausea and/or vomiting.
Prochlorperazine
Nausea and/or vomiting.
Omeprazole
Gastroesophageal reflux disease (GERD).
Docusate Sodium + Sennosides
Constipation.
Lactulose
Constipation
Interventions
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Etoposide
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
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
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
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
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
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.
MRI
Baseline and/or on completion of therapy.
CT
Baseline and/or on completion of therapy.
Biopsy
Baseline and/or on completion of therapy.
PET scan
As clinically indicated.
Laparotomy
As clinically indicated.
Ondansetron
Nausea and/or vomiting.
Prochlorperazine
Nausea and/or vomiting.
Omeprazole
Gastroesophageal reflux disease (GERD).
Docusate Sodium + Sennosides
Constipation.
Lactulose
Constipation
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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.
12 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Mark Roschewski, M.D.
Investigator
Principal Investigators
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Mark J Roschewski, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)
Locations
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Holy Cross Hospital, Fort Lauderdale
Fort Lauderdale, Florida, United States
University of Maryland, Baltimore
Baltimore, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
St. Luke's Roosevelt Hospital
New York, New York, United States
Countries
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References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
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NIH Clinical Center Detailed Web Page
Other Identifiers
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93-C-0133
Identifier Type: -
Identifier Source: secondary_id
930133
Identifier Type: -
Identifier Source: org_study_id
NCT00018980
Identifier Type: -
Identifier Source: nct_alias
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