Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma

NCT00274924 | Completed Phase 2 Results

• 3 other identifiers: CDR0000455012U10CA021115E3404
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 104

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin's lymphoma.

Conditions

Lymphoma

Keywords

contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma

Outcome Measures

Primary Outcomes (1)

• 2-year Progression-Free Survival (PFS)

  2-year progression-free survival is defined as the probability of patients who remain alive and progression free at 2 years from study entry. The method of Kaplan and Meier (1958) was used to estimate PFS.

  Assessed every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry.

Secondary Outcomes (1)

• 5-year Overall Survival

  Every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry.

Study Arms (2)

Group I (PET negative)

EXPERIMENTAL

Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine

Group II (PET positive)

EXPERIMENTAL

Patients receive R-ICE comprising rituximab IV on day 1, ifosfamide IV continuously over 24 hours and carboplatin IV over 30 minutes on day 2, and etoposide IV over 2 hours on days 1-3. Patients also receive filgrastim (G-CSF) subcutaneously once daily starting on day 4 and continuing until blood counts recover. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Biological: filgrastim; Biological: rituximab; Drug: carboplatin; Drug: cyclophosphamide; Drug: etoposide; Drug: ifosfamide

Interventions

filgrastim BIOLOGICAL

Given subcutaneously or intravenous bolus.

Also known as: G-CSF, Neupogen, recombinant-methionyl human granulocyte-colony stimulating, factor, granulocyte colony-stimulating factor, r-metHuG-CSF.

Group II (PET positive)

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan.

Group I (PET negative); Group II (PET positive)

carboplatin DRUG

Given IV

Also known as: CBDCA, Paraplatin, JM-8, NSC #241240.

Group II (PET positive)

cyclophosphamide DRUG

Given IV

Also known as: Cytoxan, Neosar, CTX, CPM.

Group I (PET negative); Group II (PET positive)

doxorubicin hydrochloride DRUG

Given IV

Also known as: Adriamycin, Rubex, Adriamycin RDF, Adriamycin PFS, hydroxydaunorubicin,, hydroxydaunomycin, ADR.

Group I (PET negative)

etoposide DRUG

Given IV

Also known as: VP-16, VePesid, epipodophyllotoxin

Group II (PET positive)

ifosfamide DRUG

Given IV

Also known as: Isophosphamide, Ifex , Mitoxan , Holoxan , Naxamide ' NSC # 109724.

Group II (PET positive)

prednisone DRUG

Taken orally

Also known as: Deltasone, Orasone, Medicorten, Panasol-S, Liquid-Pred, others.

Group I (PET negative)

vincristine DRUG

Given IV

Also known as: Oncovin, Vincasar PFS vincristine sulfate, VCR, leucocristine, LCR.

Group I (PET negative)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diffuse large B-cell non-Hodgkin's lymphoma
• Bulky stage II (bulk defined as any lesion ≥ 10 cm) or stage III or IV disease
• The following lymphoma types are excluded:
• Primary central nervous system lymphoma
• Transformed low-grade lymphoma (prior history of low-grade lymphoma or clear presence of low-grade lymphoma on histologic sections)
• Primary mediastinal B-cell lymphoma or testicular lymphoma (consolidative radiotherapy is usually indicated)
• Immunodeficiency-related lymphoma (i.e., after organ or bone marrow transplant)
• Measurable disease
• Patient must have at least one objective measurable disease site (i.e., measurable in at least 2 perpendicular parameters)
• Measurable disease in the liver is required if the liver is the only site of lymphoma involvement
• Abnormal positron emission tomography scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3
• For patients \> 50 years of age, a normal ejection fraction by ECHO or Multigated Acquisition Scan (MUGA) is required within 6 weeks prior to registration
• Absolute neutrophil count ≥ 1,500/mm\^3
• Platelet count \> 100,000/mm\^3

You may not qualify if:

• Prior chemotherapy or radiation therapy for lymphoma
• Prior anthracyclines or platinum compounds used as systemic chemotherapy
• Prior radiation therapy to the mediastinum or to ≥ 25% of the bone marrow
• Concurrent pentostatin or trastuzumab (Herceptin®)
• Pregnant or nursing
• Prior malignancy within the past 5 years unless it was in situ OR was treated with curative intent AND the patient has remained relapse-free
• HIV positive

Sponsors & Collaborators

• Eastern Cooperative Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (104)

Veterans Affairs Medical Center - Palo Alto

Palo Alto, California, 94304, United States

Location

Front Range Cancer Specialists

Fort Collins, Colorado, 80528, United States

Location

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Rush-Copley Cancer Care Center

Aurora, Illinois, 60504, United States

Location

St. Joseph Medical Center

Bloomington, Illinois, 61701, United States

Location

Graham Hospital

Canton, Illinois, 61520, United States

Location

Memorial Hospital

Carthage, Illinois, 62321, United States

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Eureka Community Hospital

Eureka, Illinois, 61530, United States

Location

Evanston Northwestern Healthcare - Evanston Hospital

Evanston, Illinois, 60201-1781, United States

Location

Galesburg Clinic, PC

Galesburg, Illinois, 61401, United States

Location

Galesburg Cottage Hospital

Galesburg, Illinois, 61401, United States

Location

Mason District Hospital

Havana, Illinois, 62644, United States

Location

Hinsdale Hematology Oncology Associates

Hinsdale, Illinois, 60521, United States

Location

Hopedale Medical Complex

Hopedale, Illinois, 61747, United States

Location

Joliet Oncology-Hematology Associates, Limited - West

Joliet, Illinois, 60435, United States

Location

McDonough District Hospital

Macomb, Illinois, 61455, United States

Location

Trinity Cancer Center at Trinity Medical Center - 7th Street Campus

Moline, Illinois, 61265, United States

Location

Unknown Facility

Moline, Illinois, 61265, United States

Location

BroMenn Regional Medical Center

Normal, Illinois, 61761, United States

Location

Community Cancer Center

Normal, Illinois, 61761, United States

Location

Community Hospital of Ottawa

Ottawa, Illinois, 61350, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, 61350, United States

Location

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, 61554, United States

Location

Proctor Hospital

Peoria, Illinois, 61614, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61615, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, 61615, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Illinois Valley Community Hospital

Peru, Illinois, 61354, United States

Location

Perry Memorial Hospital

Princeton, Illinois, 61356, United States

Location

St. Margaret's Hospital

Spring Valley, Illinois, 61362, United States

Location

Carle Cancer Center at Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Saint Anthony Memorial Health Centers

Michigan City, Indiana, 46360, United States

Location

McFarland Clinic, PC

Ames, Iowa, 50010, United States

Location

Unknown Facility

Bettendorf, Iowa, 52722, United States

Location

Mercy Capitol Hospital

Des Moines, Iowa, 50307, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309, United States

Location

John Stoddard Cancer Center at Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at John Stoddard Cancer Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at Mercy Cancer Center

Des Moines, Iowa, 50314, United States

Location

Mercy Cancer Center at Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

John Stoddard Cancer Center at Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, 51101, United States

Location

Mercy Medical Center - Sioux City

Sioux City, Iowa, 51104, United States

Location

St. Luke's Regional Medical Center

Sioux City, Iowa, 51104, United States

Location

Greater Baltimore Medical Center Cancer Center

Baltimore, Maryland, 21204, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, 48106-0995, United States

Location

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, 48106, United States

Location

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, 48123-2500, United States

Location

Genesys Hurley Cancer Institute

Flint, Michigan, 48503, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, 48236, United States

Location

Foote Memorial Hospital

Jackson, Michigan, 49201, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Sparrow Regional Cancer Center

Lansing, Michigan, 48912-1811, United States

Location

St. Mary Mercy Hospital

Livonia, Michigan, 48154, United States

Location

St. Joseph Mercy Oakland

Pontiac, Michigan, 48341-2985, United States

Location

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, 48060, United States

Location

Seton Cancer Institute at Saint Mary's - Saginaw

Saginaw, Michigan, 48601, United States

Location

St. John Macomb Hospital

Warren, Michigan, 48093, United States

Location

Duluth Clinic Cancer Center - Duluth

Duluth, Minnesota, 55805-1983, United States

Location

CCOP - Duluth

Duluth, Minnesota, 55805, United States

Location

Miller - Dwan Medical Center

Duluth, Minnesota, 55805, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

NYU Cancer Institute at New York University Medical Center

New York, New York, 10016, United States

Location

Aultman Cancer Center at Aultman Hospital

Canton, Ohio, 44710-1799, United States

Location

Christ Hospital Cancer Center

Cincinnati, Ohio, 45219, United States

Location

MetroHealth Cancer Care Center at MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, 17822-0001, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Lewistown Hospital

Lewistown, Pennsylvania, 17044, United States

Location

Cancer Center of Paoli Memorial Hospital

Paoli, Pennsylvania, 19301-1792, United States

Location

Geisinger Medical Group - Scenery Park

State College, Pennsylvania, 16801, United States

Location

Mount Nittany Medical Center

State College, Pennsylvania, 16803, United States

Location

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

Wilkes-Barre, Pennsylvania, 18711, United States

Location

CCOP - Main Line Health

Wynnewood, Pennsylvania, 19096, United States

Location

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, 19096, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Medical X-Ray Center, PC

Sioux Falls, South Dakota, 57105, United States

Location

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, 57117-5039, United States

Location

Center for Cancer Treatment & Prevention at Sacred Heart Hospital

Eau Claire, Wisconsin, 54701, United States

Location

Marshfield Clinic Cancer Care at Regional Cancer Center

Eau Claire, Wisconsin, 54701, United States

Location

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, 54601, United States

Location

Dean Medical Center - Madison

Madison, Wisconsin, 53717, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

Saint Joseph's Hospital

Marshfield, Wisconsin, 54449, United States

Location

Froedtert Hospital and Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Marshfield Clinic - Lakeland Center

Minocqua, Wisconsin, 54548, United States

Location

Ministry Medical Group at Saint Mary's Hospital

Rhinelander, Wisconsin, 54501, United States

Location

Marshfield Clinic - Indianhead Center

Rice Lake, Wisconsin, 54868, United States

Location

Saint Michael's Hospital Cancer Center

Stevens Point, Wisconsin, 54481, United States

Location

Marshfield Clinic - Wausau Center

Wausau, Wisconsin, 54401, United States

Location

Marshfield Clinic - Weston Center

Weston, Wisconsin, 54476, United States

Location

Marshfield Clinic - Wisconsin Rapids Center

Wisconsin Rapids, Wisconsin, 54494, United States

Location

Related Publications (1)

• Horning SJ, Juweid ME, Schoder H, Wiseman G, McMillan A, Swinnen LJ, Advani R, Gascoyne R, Quon A. Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study. Blood. 2010 Jan 28;115(4):775-7; quiz 918. doi: 10.1182/blood-2009-08-234351. Epub 2009 Sep 18.

  PMID: 19767508 RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Rituximab; Carboplatin; Cyclophosphamide; carboxypeptidase M; Doxorubicin; Etoposide; Podophyllotoxin; Ifosfamide; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Lignans; Benzyl Compounds; Benzene Derivatives; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG Statistical Office

617-632-3012

Study Officials

• Lode J. Swinnen, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

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: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2006
• First Posted: January 11, 2006
• Study Start: September 26, 2006
• Primary Completion: June 1, 2013
• Study Completion: March 1, 2019
• Last Updated: June 29, 2023
• Results First Posted: February 24, 2014

Record last verified: 2023-06

Locations

US (104)