Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma
NCT ID: NCT00118209
Last Updated: 2021-11-17
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
524 participants
INTERVENTIONAL
2005-05-31
2021-11-15
Brief Summary
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PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.
Detailed Description
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I. To compare the event-free survival of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone (R-CHOP) versus dose-adjusted (DA-) etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, and rituximab (EPOCH-R) chemotherapy in untreated cluster of differentiation (CD)20 positive (+) diffuse large B-cell lymphomas.
II. To develop a molecular predictor of outcome of R-CHOP and DA-EPOCH-R chemotherapy using molecular profiling.
SECONDARY OBJECTIVES:
I. To compare the response rates, overall survival and toxicity of R-CHOP versus DA-EPOCH-R.
II. To define the pharmacogenomics of untreated diffuse large B-cell lymphoma (DLBCL) and correlate clinical parameters (toxicity, response, survival outcomes and laboratory results) with molecular profiling.
III. To assess the use of molecular profiling for pathological diagnosis. IV. To identify new therapeutic targets using molecular profiling. V. To perform a comprehensive analysis of somatic alterations to the tumor genome and to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient.
VI. To identify biomarkers of response to chemotherapy by fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging that are predictive of histopathologic remissions and survival in patients with stage I (mediastinal), II, III, or IV untreated DLBCL.
VII. To evaluate the use of semiquantitative measurements of FDG uptake in defining FDG-PET/CT based biomarkers of response to chemotherapy in patients with DLBCL.
VIII. To determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response.
IX. To establish a standardized protocol for FDG-PET/CT image acquisition. X. To determine additional FDG-PET/CT parameters (e.g., the ratio of tumor maximum standard uptake value \[SUVmax\] to liver SUVmean; SUVs corrected for body surface area and lean body mass; nuclear medicine physician's assessment) and evaluate their utility in refining FDG-PET/CT based biomarkers of response to therapy.
XI. To evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A - R-CHOP
Patients receive the following treatment:
* Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to CHOP chemotherapy
* Cyclophosphamide 750 mg/m\^2 IV on Day 1
* Doxorubicin 50 mg/m\^2 IV on Day 1
* Vincristine 1.4 mg/m\^2 IV (2 mg cap) on Day 1
* Prednisone 40 mg/m\^2/day PO on Days 1-5
* filgrastim or pegfilgrastim as defined in the protocol
Required ancillary medications is administered during all cycles as defined in the protocol.
Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.
rituximab
IV
cyclophosphamide
IV
doxorubicin
IV or CIVI
vincristine
IV or CIVI
prednisone
oral
filgrastim
IV
pegfilgrastim
IV
Arm B - DA-EPOCH-R
Patients receive the following treatment:
Cycle 1 Doses:
* Rituximab 375 mg/m\^2 IV infusion on Day 1 prior to EPOCH chemotherapy
* Doxorubicin 10 mg/m\^2/day CIVI on Days 1-4
* Etoposide 50 mg/m\^2/day CIVI on Days 1-4
* Vincristine 0.4 mg/m\^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)
* Cyclophosphamide 750 mg/m\^2 IV on Day 5 (following completion of 96 hour infusions)
* Prednisone 60 mg/m\^2 PO BID on Days 1-5
* Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC \> 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle.
Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.
Required ancillary medications are administered during all cycles as defined in the protocol.
Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.
rituximab
IV
cyclophosphamide
IV
doxorubicin
IV or CIVI
vincristine
IV or CIVI
prednisone
oral
etoposide
CIVI
filgrastim
IV
Interventions
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rituximab
IV
cyclophosphamide
IV
doxorubicin
IV or CIVI
vincristine
IV or CIVI
prednisone
oral
etoposide
CIVI
filgrastim
IV
pegfilgrastim
IV
Eligibility Criteria
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Inclusion Criteria
* Diagnosis should be based on an adequate tissue sample, including open biopsy or core needle biopsy.
* Needle aspiration for primary diagnosis is unacceptable.
* Patients must have one of the following WHO classification subtypes:
* Diffuse large B-cell lymphoma (includes morphological variants: centroblastic, immunoblastic, T-cell/histiocyte rich, and anaplastic)
* Mediastinal (thymic) large B-cell lymphoma
* Intravascular large B-cell lymphoma
* Note: Failure to submit a pathology block within 60 days of patient registration will be considered a major protocol violation.
* Fresh (frozen) tumor biopsy must be available or attempted. A frozen tumor biopsy equivalent to a minimum of four at least 16 gauge needle cores is an important component of this study.
* Patients without adequate frozen material should have a biopsy performed to obtain material.
* If a biopsy is performed and does not yield adequate material, the patient is still eligible for the study. If a biopsy cannot be done safely, the patient may still be eligible for the study if permission is granted.
* Note: This study does not allow concurrent radiation unless a patient has a documented CNS treatment failure with no systemic failure.
2. No prior cytotoxic chemotherapy or rituximab. Patients may be entered if they have received prior limited field radiation therapy or a short course of glucocorticoids (\< 10 days) for an urgent local disease complication at diagnosis (e.g., cord compression, SVC syndrome). Patients who have received chemotherapy for prior malignancies are not eligible.
3. Age ≥ 18 years
4. ECOG Performance Status 0-2
5. No active ischemic heart disease or congestive heart failure. If there is suspicion of cardiac disease, a cardiac ejection fraction must show LVEF \> 45%, but the study is not required
6. No known lymphomatous involvement of the CNS. A lumbar puncture prior to study is not required in the absence of neurological symptoms
7. No known HIV disease. Patients with a history of intravenous drug abuse or any other behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Patients who test positive or who are known to be infected are not eligible.
8. Non pregnant and non-nursing. Treatment would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective form of contraception.
9. Patients with active medical processes (e.g., uncontrolled bacterial or viral infection, bleeding) not related to their lymphoma should be excluded.
10. Required Initial Laboratory Values (unless non-Hodgkin lymphoma):
* ANC ≥ 1000/μL
* Platelets ≥ 100,000/μL
* Creatinine≤ 1.5 mg/dL or creatinine clearance ≥ 50 cc/min
* Total Bilirubin ≤ 2 mg/dL (unless a history of Gilbert's Disease)
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Alliance for Clinical Trials in Oncology
OTHER
Responsible Party
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Principal Investigators
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Wyndham H. Wilson, MD, PhD
Role: STUDY_CHAIR
National Cancer Institute (NCI)
Andrew D. Zelenetz, MD, PhD
Role: STUDY_CHAIR
Memorial Sloan Kettering Cancer Center
Locations
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Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States
Camino Medical Group - Treatment Center
Mountain View, California, United States
Palo Alto Medical Foundation
Palo Alto, California, United States
Naval Medical Center - San Diego
San Diego, California, United States
Saint Helena Hospital
St. Helena, California, United States
Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut, United States
CCOP - Christiana Care Health Services
Newark, Delaware, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States
University of Illinois Cancer Center
Chicago, Illinois, United States
Creticos Cancer Center at Advocate Illinois Masonic Medical Center
Chicago, Illinois, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States
National Naval Medical Center
Bethesda, Maryland, United States
NIH - Warren Grant Magnuson Clinical Center
Bethesda, Maryland, United States
Providence Cancer Institute at Providence Hospital - Southfield Campus
Southfield, Michigan, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, United States
Christian Hospital Northeast-Northwest
St Louis, Missouri, United States
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
Concord, New Hampshire, United States
New Hampshire Oncology - Hematology, PA - Hooksett
Hooksett, New Hampshire, United States
Charles R. Wood Cancer Center at Glens Falls Hospital
Glens Falls, New York, United States
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States
Kinston Medical Specialists
Kinston, North Carolina, United States
Iredell Memorial Hospital
Statesville, North Carolina, United States
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
Altru Cancer Center at Altru Hospital
Grand Forks, North Dakota, United States
Mercy Cancer Center at Mercy Medical Center
Canton, Ohio, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Geisinger Cancer Institute at Geisinger Health
Danville, Pennsylvania, United States
Easton Regional Cancer Center at Easton Hospital
Easton, Pennsylvania, United States
Geisinger Hazleton Cancer Center
Hazleton, Pennsylvania, United States
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, United States
Mountainview Medical
Berlin Corners, Vermont, United States
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States
Madigan Army Medical Center - Tacoma
Tacoma, Washington, United States
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
Morgantown, West Virginia, United States
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States
Saint Joseph's Hospital
Marshfield, Wisconsin, United States
Marshfield Clinic - Lakeland Center
Minocqua, Wisconsin, United States
Ministry Medical Group at Saint Mary's Hospital
Rhinelander, Wisconsin, United States
Marshfield Clinic - Indianhead Center
Rice Lake, Wisconsin, United States
Marshfield Clinic at Saint Michael's Hospital
Stevens Point, Wisconsin, United States
Saint Michael's Hospital Cancer Center
Stevens Point, Wisconsin, United States
Marshfield Clinic - Weston Center
Weston, Wisconsin, United States
Countries
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References
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Morrison VA, Le-Rademacher J, Bobek O, Satele D, Leonard JP, Jatoi A. Association of age and performance status with adverse events in older adults with diffuse large B-cell lymphoma receiving frontline R-CHOP therapy: Alliance 151930, a secondary analysis of the phase III trial CALGB 50303. J Geriatr Oncol. 2025 Mar;16(2):102185. doi: 10.1016/j.jgo.2025.102185. Epub 2025 Jan 13.
Schoder H, Polley MC, Knopp MV, Hall N, Kostakoglu L, Zhang J, Higley HR, Kelloff G, Liu H, Zelenetz AD, Cheson BD, Wagner-Johnston N, Kahl BS, Friedberg JW, Hsi ED, Leonard JP, Schwartz LH, Wilson WH, Bartlett NL. Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial. Blood. 2020 Jun 18;135(25):2224-2234. doi: 10.1182/blood.2019003277.
Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schoder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. doi: 10.1200/JCO.18.01994. Epub 2019 Apr 2.
Barta SK, Lee JY, Kaplan LD, Noy A, Sparano JA. Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Cancer. 2012 Aug 15;118(16):3977-83. doi: 10.1002/cncr.26723. Epub 2011 Dec 16.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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CDR0000433265
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2009-00480
Identifier Type: REGISTRY
Identifier Source: secondary_id
CALGB-50303
Identifier Type: -
Identifier Source: org_study_id
NCT00234351
Identifier Type: -
Identifier Source: nct_alias