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Large B Cell LymphomaPhase 3NCT00118209

Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma

A Phase 3 study testing rituximab, cyclophosphamide and doxorubicin in people with Large B Cell Lymphoma, run by Alliance for Clinical Trials in Oncology at 47 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

This randomized phase III trial studies rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Large B Cell Lymphoma
What is being tested?
rituximab, cyclophosphamide and doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
524 participants
Where
47 sitesUnited States
Study dates
May 2005to 15 Nov 2021
Phase
Phase 3
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult
  1. Histologically documented de novo CD20+ DLBCL with stage II, III or IV disease.
  • Stage I primary mediastinal (thymic) DLBCL is also eligible.
  • Patients with an underlying low-grade lymphoma, such as a transformed lymphoma or low-grade lymphoma in the bone marrow, are not eligible.
  • 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.
  1. 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.
  2. Age ≥ 18 years
  3. ECOG Performance Status 0-2
  4. 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
  5. No known lymphomatous involvement of the CNS. A lumbar puncture prior to study is not required in the absence of neurological symptoms
  6. 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.
  7. 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.
  8. Patients with active medical processes (e.g., uncontrolled bacterial or viral infection, bleeding) not related to their lymphoma should be excluded.
  9. 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)

Trial locations and contacts

47 sites in 1 country.

47 sites in 1 country

United States47 sites

  • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

    Baltimore, Maryland, 21215

  • Mountainview Medical

    Berlin Corners, Vermont, 05602

  • National Naval Medical Center

    Bethesda, Maryland, 20889-5600

  • NIH - Warren Grant Magnuson Clinical Center

    Bethesda, Maryland, 20892-1182

  • Mercy Cancer Center at Mercy Medical Center

    Canton, Ohio, 44708

  • Presbyterian Cancer Center at Presbyterian Hospital

    Charlotte, North Carolina, 28233-3549

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

    Chicago, Illinois, 60611-3013

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612-7243

  • Creticos Cancer Center at Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210-1240

  • New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care

    Concord, New Hampshire, 03301

  • Geisinger Cancer Institute at Geisinger Health

    Danville, Pennsylvania, 17822-0001

  • Easton Regional Cancer Center at Easton Hospital

    Easton, Pennsylvania, 18042

  • Charles R. Wood Cancer Center at Glens Falls Hospital

    Glens Falls, New York, 12801

  • Altru Cancer Center at Altru Hospital

    Grand Forks, North Dakota, 58201

  • Geisinger Hazleton Cancer Center

    Hazleton, Pennsylvania, 18201

  • Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • New Hampshire Oncology - Hematology, PA - Hooksett

    Hooksett, New Hampshire, 03106

  • Kinston Medical Specialists

    Kinston, North Carolina, 28501

  • Rebecca and John Moores UCSD Cancer Center

    La Jolla, California, 92093-0658

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin, 54449

  • Saint Joseph's Hospital

    Marshfield, Wisconsin, 54449

  • Cardinal Bernardin Cancer Center at Loyola University Medical Center

    Maywood, Illinois, 60153

  • Marshfield Clinic - Lakeland Center

    Minocqua, Wisconsin, 54548

  • Mary Babb Randolph Cancer Center at West Virginia University Hospitals

    Morgantown, West Virginia, 26506

  • Camino Medical Group - Treatment Center

    Mountain View, California, 94040

  • New York Weill Cornell Cancer Center at Cornell University

    New York, New York, 10021

  • CCOP - Christiana Care Health Services

    Newark, Delaware, 19713

  • Eastern Connecticut Hematology and Oncology Associates

    Norwich, Connecticut, 06360

  • Palo Alto Medical Foundation

    Palo Alto, California, 94301

  • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

    Pittsburgh, Pennsylvania, 15224-1791

  • Ministry Medical Group at Saint Mary's Hospital

    Rhinelander, Wisconsin, 54501

  • Marshfield Clinic - Indianhead Center

    Rice Lake, Wisconsin, 54868

  • Virginia Commonwealth University Massey Cancer Center

    Richmond, Virginia, 23298-0037

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

    Rochester, New York, 14642

  • Naval Medical Center - San Diego

    San Diego, California, 92134

  • Providence Cancer Institute at Providence Hospital - Southfield Campus

    Southfield, Michigan, 48075

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • Christian Hospital Northeast-Northwest

    St Louis, Missouri, 63136

  • Saint Helena Hospital

    St. Helena, California, 94574

  • Iredell Memorial Hospital

    Statesville, North Carolina, 28677

  • Marshfield Clinic at Saint Michael's Hospital

    Stevens Point, Wisconsin, 54481

  • Saint Michael's Hospital Cancer Center

    Stevens Point, Wisconsin, 54481

  • Madigan Army Medical Center - Tacoma

    Tacoma, Washington, 98431

  • Marshfield Clinic - Weston Center

    Weston, Wisconsin, 54476

  • Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

    Wilkes-Barre, Pennsylvania, 18711

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157-1096

Other trials in United States

About this study

Official title: Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas

This randomized phase III trial studies rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma.

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

What participants receive

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

Study groups in NCT00118209
Study groupRoleWhat they receive
Arm A - R-CHOPActive comparatorPatients 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.
Receives: Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin; Drug: vincristine; Drug: prednisone; Drug: filgrastim; Drug: pegfilgrastim
Arm B - DA-EPOCH-RExperimentalPatients 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.
Receives: Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin; Drug: vincristine; Drug: prednisone; Drug: etoposide; Drug: filgrastim

What is being measured

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

  1. Progression-Free Survival Rate at 2 and 5 Years

    Progression-free survival (PFS) is defined as the time from randomization to progression, relapse, or death from any cause, whichever occurred first. Progression (PD) or Relapse>

    • ≥ 50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders.>
    • Appearance of any new lesion during or after completion of therapy.>
    • PET+ is not a criterion for progressive disease. Patients only with PET+ findings must have evidence of progression on CT or biopsy proven.>

    The PFS rate (percentage of participants who are alive and progression-free) at 2 and 5 years Kaplan Meier estimates and 95% Confidence Intervals are reported below.

    Measured: Up to 5 years post-registration

Secondary outcomes (2)

  1. Response Rate

    The overall response rate is defined as the percentage of participants with a response (Complete Response or Partial Response)

    Measured: Up to 5 years post-registration

  2. Overall Survival Rate at 2 and 5 Years

    Overall survival is defined as the time from randomization to death due to any cause. The overall survival (OS) rate (percentage of participants who are still alive) at 2 and 5 years Kaplan Meier estimates and 95% confidence intervals are reported below.

    Measured: Up to 5 years post-registration

Timeline

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

  1. First posted11 Jul 2005 (estimated)
  2. Study startMay 2005
  3. Primary completionOct 2017
  4. Study completion15 Nov 2021

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
524 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00118209
Sponsor's protocol ID
CALGB-50303
Other IDs
CDR0000433265, NCI-2009-00480, U10CA031946, U10CA180821
Status last verified
Nov 2021
First submitted
8 Jul 2005
Last updated
17 Nov 2021
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 39809075

  • 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.

    PubMed 32232481

  • 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.

    PubMed 30939090

  • 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.

    PubMed 22180164

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rituximab, cyclophosphamide and doxorubicin in people with Large B Cell Lymphoma, run by Alliance for Clinical Trials in Oncology at 47 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?

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 17 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 17 Apr 2020). 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?

Progression-Free Survival Rate at 2 and 5 Years (time frame: Up to 5 years post-registration). 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 NCT00118209, which also lists 4 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 17 Nov 2021; AzTrials last refreshed its copy on 26 Oct 2026.

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