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

Phase 2

Completed

• Conditions: Lymphoma
• Interventions: Biological: rituximab; Biological: filgrastim; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: carboplatin; Drug: prednisone; Drug: etoposide; Drug: vincristine; Drug: ifosfamide

• Registration Number: NCT00274924
• Lead Sponsor: Eastern Cooperative Oncology Group

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.

Detailed Description

OBJECTIVES:

Primary

* Determine the 2-year progression-free survival (PFS) rate after treatment with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in patients with bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma who remain positron emission tomography (PET)-positive after 3 courses of rituximab, cyclophosphamide, vincristine, doxorubicin hydrochloride, and prednisone.

Secondary

* Determine the proportion of mid-treatment PET-positive patients who become PET-negative after 4 courses of R-ICE.

* Determine the PFS of mid-treatment PET-negative patients treated with these regimens.

* Determine the overall survival of patients treated with these regimens.

* Determine the toxicity of these regimens in these patients.

OUTLINE:

* Rituximab and Combination Chemotherapy (R-CHOP: R= Rituximab, C= Cyclophosphamide, H= Doxorubicin Hydrochloride (Hydroxydaunomycin), O= Vincristine Sulfate (Oncovin), P= Prednisone): 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 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo fludeoxyglucose F18 positron emission tomography (PET) scanning and conventional restaging during course 3. Based on the PET results, patients are assigned to 1 of 2 treatment groups.

* Group I (PET negative): Patients receive 2 more courses of R-CHOP as above in the absence of disease progression or unacceptable toxicity.

* Group II (PET positive): Patients receive Rituximab 375 mg/m2 IV Day 1, Ifosfamide 5000 mg/m2 IV over 24 hours Day 2, Carboplatin AUC 5 (max: 800 mg) IV Day 2, Etoposide 100 mg/m2 IV Days 1, 2, 3 (R-ICE), Mesna 5000 mg/m2 IV over 24 hours Day 2, and Filgrastim 5 mcg/kg/day subcutaneous (SC) Day 4 until absolute neutrophil count (ANC) recovery every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 10 years from the date of study entry.

ACCRUAL: A total of 100 patients were accrued for this study.

Study Timeline

• Study First Submitted: 2006-01-10
• Study First Submitted QC: 2006-01-10
• Study First Posted: 2006-01-11
• Study Start: 2006-09-26
• Primary Completion: 2013-06
• Results First Submitted: 2014-01-09
• Results First Submitted QC: 2014-01-09
• Results First Posted: 2014-02-24
• Study Completion: 2019-03
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-15
• Last Update Posted: 2023-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (PET negative)	cyclophosphamide	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.
Group I (PET negative)	prednisone	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.
Group II (PET positive)	etoposide	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.
Group I (PET negative)	rituximab	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.
Group I (PET negative)	doxorubicin hydrochloride	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.
Group II (PET positive)	carboplatin	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.
Group II (PET positive)	cyclophosphamide	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.
Group II (PET positive)	filgrastim	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.
Group II (PET positive)	rituximab	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.
Group I (PET negative)	vincristine	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.
Group II (PET positive)	ifosfamide	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.

Primary Outcome Measures

Name	Time	Method
2-year Progression-Free Survival (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.	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.

Secondary Outcome Measures

Name	Time	Method
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.	5-year overall survival is defined as the probability of patients who remain alive at 5 years from study entry. The method of Kaplan and Meier (1958) was used to estimate overall survival.

Trial Locations

Locations (102)

Robert H. Lurie Comprehensive Cancer Center at Northwestern University; 🇺🇸 Chicago, Illinois, United States

Mason District Hospital; 🇺🇸 Havana, Illinois, United States

Greater Baltimore Medical Center Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

MetroHealth Cancer Care Center at MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

Christ Hospital Cancer Center; 🇺🇸 Cincinnati, Ohio, United States

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States

Medical College of Wisconsin Cancer Center; 🇺🇸 Milwaukee, Wisconsin, United States

Veterans Affairs Medical Center - Palo Alto; 🇺🇸 Palo Alto, California, United States

Front Range Cancer Specialists; 🇺🇸 Fort Collins, Colorado, United States

Mayo Clinic - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Baptist Cancer Institute - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Rush-Copley Cancer Care Center; 🇺🇸 Aurora, Illinois, United States

St. Joseph Medical Center; 🇺🇸 Bloomington, Illinois, United States

Graham Hospital; 🇺🇸 Canton, Illinois, United States

Eureka Community Hospital; 🇺🇸 Eureka, Illinois, United States

Galesburg Clinic, PC; 🇺🇸 Galesburg, Illinois, United States

Hinsdale Hematology Oncology Associates; 🇺🇸 Hinsdale, Illinois, United States

Joliet Oncology-Hematology Associates, Limited - West; 🇺🇸 Joliet, Illinois, United States

McDonough District Hospital; 🇺🇸 Macomb, Illinois, United States

Community Cancer Center; 🇺🇸 Normal, Illinois, United States

Hopedale Medical Complex; 🇺🇸 Hopedale, Illinois, United States

BroMenn Regional Medical Center; 🇺🇸 Normal, Illinois, United States

Cancer Treatment Center at Pekin Hospital; 🇺🇸 Pekin, Illinois, United States

Community Hospital of Ottawa; 🇺🇸 Ottawa, Illinois, United States

Trinity Cancer Center at Trinity Medical Center - 7th Street Campus; 🇺🇸 Moline, Illinois, United States

Proctor Hospital; 🇺🇸 Peoria, Illinois, United States

Oncology Hematology Associates of Central Illinois, PC - Peoria; 🇺🇸 Peoria, Illinois, United States

Oncology Hematology Associates of Central Illinois, PC - Ottawa; 🇺🇸 Ottawa, Illinois, United States

CCOP - Illinois Oncology Research Association; 🇺🇸 Peoria, Illinois, United States

Illinois Valley Community Hospital; 🇺🇸 Peru, Illinois, United States

Methodist Medical Center of Illinois; 🇺🇸 Peoria, Illinois, United States

OSF St. Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

Perry Memorial Hospital; 🇺🇸 Princeton, Illinois, United States

Carle Cancer Center at Carle Foundation Hospital; 🇺🇸 Urbana, Illinois, United States

CCOP - Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

St. Margaret's Hospital; 🇺🇸 Spring Valley, Illinois, United States

McFarland Clinic, PC; 🇺🇸 Ames, Iowa, United States

Saint Anthony Memorial Health Centers; 🇺🇸 Michigan City, Indiana, United States

Siouxland Hematology-Oncology Associates, LLP; 🇺🇸 Sioux City, Iowa, United States

Mercy Medical Center - Sioux City; 🇺🇸 Sioux City, Iowa, United States

St. Luke's Regional Medical Center; 🇺🇸 Sioux City, Iowa, United States

Oakwood Cancer Center at Oakwood Hospital and Medical Center; 🇺🇸 Dearborn, Michigan, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center; 🇺🇸 Grosse Pointe Woods, Michigan, United States

Genesys Hurley Cancer Institute; 🇺🇸 Flint, Michigan, United States

Hurley Medical Center; 🇺🇸 Flint, Michigan, United States

Foote Memorial Hospital; 🇺🇸 Jackson, Michigan, United States

Borgess Medical Center; 🇺🇸 Kalamazoo, Michigan, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

Bronson Methodist Hospital; 🇺🇸 Kalamazoo, Michigan, United States

St. Mary Mercy Hospital; 🇺🇸 Livonia, Michigan, United States

Sparrow Regional Cancer Center; 🇺🇸 Lansing, Michigan, United States

Seton Cancer Institute at Saint Mary's - Saginaw; 🇺🇸 Saginaw, Michigan, United States

Mercy Regional Cancer Center at Mercy Hospital; 🇺🇸 Port Huron, Michigan, United States

St. Joseph Mercy Oakland; 🇺🇸 Pontiac, Michigan, United States

St. John Macomb Hospital; 🇺🇸 Warren, Michigan, United States

Duluth Clinic Cancer Center - Duluth; 🇺🇸 Duluth, Minnesota, United States

Miller - Dwan Medical Center; 🇺🇸 Duluth, Minnesota, United States

Newark Beth Israel Medical Center; 🇺🇸 Newark, New Jersey, United States

SUNY Downstate Medical Center; 🇺🇸 Brooklyn, New York, United States

NYU Cancer Institute at New York University Medical Center; 🇺🇸 New York, New York, United States

Aultman Cancer Center at Aultman Hospital; 🇺🇸 Canton, Ohio, United States

Bryn Mawr Hospital; 🇺🇸 Bryn Mawr, Pennsylvania, United States

Lewistown Hospital; 🇺🇸 Lewistown, Pennsylvania, United States

Cancer Center of Paoli Memorial Hospital; 🇺🇸 Paoli, Pennsylvania, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

Geisinger Medical Group - Scenery Park; 🇺🇸 State College, Pennsylvania, United States

CCOP - Main Line Health; 🇺🇸 Wynnewood, Pennsylvania, United States

Lankenau Cancer Center at Lankenau Hospital; 🇺🇸 Wynnewood, Pennsylvania, United States

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center; 🇺🇸 Wilkes-Barre, Pennsylvania, United States

Sanford Cancer Center at Sanford USD Medical Center; 🇺🇸 Sioux Falls, South Dakota, United States

Medical X-Ray Center, PC; 🇺🇸 Sioux Falls, South Dakota, United States

Center for Cancer Treatment & Prevention at Sacred Heart Hospital; 🇺🇸 Eau Claire, Wisconsin, United States

Gundersen Lutheran Center for Cancer and Blood; 🇺🇸 La Crosse, Wisconsin, United States

Marshfield Clinic Cancer Care at Regional Cancer Center; 🇺🇸 Eau Claire, Wisconsin, United States

Saint Joseph's Hospital; 🇺🇸 Marshfield, Wisconsin, United States

Marshfield Clinic - Marshfield Center; 🇺🇸 Marshfield, Wisconsin, United States

Froedtert Hospital and Medical College of Wisconsin; 🇺🇸 Milwaukee, 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 - Wausau Center; 🇺🇸 Wausau, Wisconsin, United States

Marshfield Clinic - Wisconsin Rapids Center; 🇺🇸 Wisconsin Rapids, Wisconsin, United States

CCOP - Duluth; 🇺🇸 Duluth, Minnesota, United States

Mount Nittany Medical Center; 🇺🇸 State College, Pennsylvania, United States

Memorial Hospital; 🇺🇸 Carthage, Illinois, United States

Evanston Northwestern Healthcare - Evanston Hospital; 🇺🇸 Evanston, Illinois, United States

Galesburg Cottage Hospital; 🇺🇸 Galesburg, Illinois, United States

Geisinger Cancer Institute at Geisinger Health; 🇺🇸 Danville, Pennsylvania, United States

Saint Michael's Hospital Cancer Center; 🇺🇸 Stevens Point, Wisconsin, United States

Marshfield Clinic - Weston Center; 🇺🇸 Weston, Wisconsin, United States

Saint Joseph Mercy Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

CCOP - Michigan Cancer Research Consortium; 🇺🇸 Ann Arbor, Michigan, United States

Mercy Capitol Hospital; 🇺🇸 Des Moines, Iowa, United States

CCOP - Iowa Oncology Research Association; 🇺🇸 Des Moines, Iowa, United States

John Stoddard Cancer Center at Iowa Methodist Medical Center; 🇺🇸 Des Moines, Iowa, United States

Medical Oncology and Hematology Associates at John Stoddard Cancer Center; 🇺🇸 Des Moines, Iowa, United States

Medical Oncology and Hematology Associates at Mercy Cancer Center; 🇺🇸 Des Moines, Iowa, United States

Mercy Cancer Center at Mercy Medical Center - Des Moines; 🇺🇸 Des Moines, Iowa, United States

John Stoddard Cancer Center at Iowa Lutheran Hospital; 🇺🇸 Des Moines, Iowa, United States

Dean Medical Center - Madison; 🇺🇸 Madison, Wisconsin, United States