Clinical trial NCT00274924: Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma
Official title: Response-Adapted Therapy for Aggressive Non-Hodgkin's Lymphomas Based on Early [18F] FDG-PET Scanning
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 2-year Progression-Free Survival (PFS)
timeFrame: 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:
measure: 5-year Overall Survival
timeFrame: 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.
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center - Palo Alto
state: California
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare - Evanston Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Moline
country: United States
facility: Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
state: Illinois
city: Moline
country: United States
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Bettendorf
country: United States
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Duluth
country: United States
facility: Duluth Clinic Cancer Center - Duluth
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Duluth
country: United States
facility: Miller - Dwan Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Canton
country: United States
facility: Aultman Cancer Center at Aultman Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Christ Hospital Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Cancer Center of Paoli Memorial Hospital
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - Main Line Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Eau Claire
country: United States
facility: Center for Cancer Treatment & Prevention at Sacred Heart Hospital
state: Wisconsin
city: Eau Claire
country: United States
facility: Marshfield Clinic Cancer Care at Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Madison
country: United States
facility: Dean Medical Center - Madison
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Marshfield
country: United States
facility: Saint Joseph's Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital and Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic - Lakeland Center
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group at Saint Mary's Hospital
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Clinic - Indianhead Center
state: Wisconsin
city: Stevens Point
country: United States
facility: Saint Michael's Hospital Cancer Center
state: Wisconsin
city: Wausau
country: United States
facility: Marshfield Clinic - Wausau Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Clinic - Weston Center
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Marshfield Clinic - Wisconsin Rapids Center
state: Wisconsin
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Lode J. Swinnen, MD
role: STUDY_CHAIR
References:
citation: 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.