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

Lymphoma Clinical Trial

Official title:

Response-Adapted Therapy for Aggressive Non-Hodgkin's Lymphomas Based on Early [18F] FDG-PET Scanning

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00274924
• Other study ID #: CDR0000455012
• Secondary ID: U10CA021115E3404
• Status: Completed
• Phase: Phase 2
• Start date: September 26, 2006
• Est. completion date: March 2019

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: March 2019
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

INCLUSION CRITERIA:

• 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

• Creatinine < 2.0 mg/dL

• Bilirubin < 2 mg/dL (may be up to 3.0 mg/dL if due to liver involvement by lymphoma)

EXCLUSION CRITERIA:

• 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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• filgrastim
Given subcutaneously or intravenous bolus.
• rituximab
Given IV

Drug:
• carboplatin
Given IV
• cyclophosphamide
Given IV
• doxorubicin hydrochloride
Given IV
• etoposide
Given IV
• ifosfamide
Given IV
• prednisone
Taken orally
• vincristine
Given IV

Locations

Country	Name	City	State
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Rush-Copley Cancer Care Center	Aurora	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	St. Joseph Medical Center	Bloomington	Illinois
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Christ Hospital Cancer Center	Cincinnati	Ohio
United States	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	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	Mercy Capitol Hospital	Des Moines	Iowa
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin
United States	Eureka Community Hospital	Eureka	Illinois
United States	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Mason District Hospital	Havana	Illinois
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	McDonough District Hospital	Macomb	Illinois
United States	Dean Medical Center - Madison	Madison	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	St. John Macomb Hospital	Warren	Michigan
United States	Marshfield Clinic - Wausau Center	Wausau	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & 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 On — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	5-year Overall Survival	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.	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.