RATIONALE: Monoclonal antibodies such as yttrium Y 90 ibritumomab tiuxetan and rituximab can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of combining yttrium Y 90 ibritumomab tiuxetan with rituximab in treating patients who have progressive non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult immunoblastic large cell lymphoma	Drug: rituximab  Drug: yttrium Y 90 ibritumomab tiuxetan  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: radiation therapy  Procedure: radioimmunotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of yttrium Y 90 ibritumomab tiuxetan and rituximab, in terms of overall response rate (complete, unconfirmed complete, and partial) and duration of response, in patients with transformed CD20+ B-cell non-Hodgkin's lymphoma.
• Determine the safety of this regimen in these patients.
• Determine the event-free survival and time to treatment progression in patients treated with this regimen.
• Determine the immunogenicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV followed within 4 hours by indium In 111 ibritumomab tiuxetan IV (for imaging) over 10 minutes on day 1. Patients undergo 2 (or 3 if needed) imaging scans between days 1-5. In the absence of altered biodistribution, patients receive rituximab IV followed within 4 hours by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8.

Patients are followed monthly for 3 months, every 3 months for 2 years, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 18-24 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed transformed CD20+ B-cell non-Hodgkin's lymphoma (NHL)
• Transformation defined as:
• Progression to a more aggressive diffuse lymphoma, excluding conversion to a more aggressive grade of follicular lymphoma (e.g., WHO/REAL follicular center, large, grade III NHL)
• Initial large cell follicular lymphoma must progress to a diffuse large cell lymphoma
• De novo transformed NHL ineligible
• Requiring treatment as determined by any of the following characteristics:
• An increase in overall tumor size
• Presence of B symptoms
• Presence of masses that are causing ongoing clinical symptomatology
• Must have less than 25% bone marrow involvement with lymphoma
• Must have received and either relapsed or failed to respond to prior therapy for initial low grade or follicular NHL
• Must have bidimensionally measurable disease defined as:
• Greater than 2 cm OR 1.5 cm if 0.5 cm slices are used during spiral CT scan
• Nonmeasurable disease includes any of the following:
• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural or pericardial effusion
• Inflammatory breast disease
• Lymphangitis cutis/pulmonis
• Abdominal masses that are not confirmed and followed by imaging techniques
• Cystic lesions
• Lesions that are situated in a previously irradiated area
• No expected impairment in bone marrrow reserve meeting any of the following criteria:
• Platelet count less than 150,000/mm^3
• Hypocellular bone marrow (less than 15% cellularity)
• Marked reduction in bone marrow precursors of one or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid)
• History of failed stem cell collection
• Patients with peritoneal invasion and/or ascites with positive cytology for lymphoma OR pleural invasion and/or effusion with positive cytology for lymphoma are eligible only if their effusion or ascites can be tapped dry
• No significant remaining malignant effusion or ascites at the time of study drug administration
• No known meningeal lymphoma or known parenchymal CNS lymphoma NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 1,500/mm^3
• Lymphocyte count no greater than 5,000/mm^3
• Platelet count at least 150,000/mm^3

Hepatic

• Bilirubin no greater than 2.0 mg/dL

Renal

• Creatinine no greater than 2.0 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 year after study treatment
• HIV negative
• No other malignancy except nonmelanoma skin cancer unless patient has completed therapy and is considered to be at less than 30% risk of relapse
• No human anti-mouse antibody (HAMA) reactivity (patients with prior exposure to murine antibodies)

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Radiotherapy
• At least 3 weeks since prior anticancer immunotherapy (6 weeks for rituximab) and recovered
• More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• No prior myeloablative therapy with bone marrow transplantation or peripheral blood stem cell rescue

Chemotherapy

• See Biologic therapy
• At least 3 weeks since prior anticancer chemotherapy (6 weeks for nitrosourea or mitomycin) and recovered

Endocrine therapy

• No concurrent systemic corticosteroids with either of the following dose schedules:
• No greater than 50 mg of prednisone as a single dose (or equivalent)
• No greater than 50 mg of prednisone per dose (or equivalent) for more than 6 doses

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior anticancer radiotherapy and recovered
• No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan
• No prior external beam radiotherapy to more than 25% of active bone marrow (involved field or regional)

Surgery

• At least 3 weeks since prior anticancer surgery and recovered
• More than 4 weeks since prior major surgery (other than diagnostic surgery)

Other

• At least 3 weeks since other prior anticancer therapy and recovered

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States; Recruiting
California
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States; Recruiting
      Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States; Recruiting
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States; Recruiting
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5001,  United States; Recruiting
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States; Recruiting
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States; Recruiting
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States; Recruiting
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States; Recruiting
      Palm Beach Cancer Institute - West Palm Beach, West Palm Beach,  Florida,  33401,  United States; Recruiting
Illinois
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Center for Cancer Care at OSF Saint Anthony Medical Center, Rockford,  Illinois,  61108,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      UMASS Memorial Cancer Center - University Campus, Worcester,  Massachusetts,  01655,  United States; Recruiting
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States; Recruiting
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States; Recruiting
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States; Recruiting
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States; Recruiting
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States; Recruiting
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States; Recruiting
North Carolina
      Cape Fear Valley Medical Center, Fayetteville,  North Carolina,  28302-2000,  United States; Recruiting
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Lenoir Memorial Cancer Center, Kinston,  North Carolina,  28503-1678,  United States; Recruiting
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States; Recruiting
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States; Recruiting
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805-9913,  United States; Recruiting
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States; Recruiting
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Pennsylvania
      Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States; Recruiting
Rhode Island
      Miriam Hospital at Lifespan, Providence,  Rhode Island,  02906,  United States; Recruiting
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-8852,  United States; Recruiting
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States; Recruiting
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States; Recruiting
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States; Recruiting
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States; Recruiting
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States; Recruiting
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States; Recruiting
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States; Recruiting
Wisconsin
      Ministry Medical Group at Saint Mary's Hospital, Rhinelander,  Wisconsin,  54501,  United States; Recruiting
Canada, Quebec
      McGill Cancer Centre at McGill University, Montreal,  Quebec,  H2W 1S6,  Canada; Recruiting
Puerto Rico
      Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus, San Juan,  00936-5067,  Puerto Rico; Recruiting

Study chairs or principal investigators

Thomas C. Shea, MD,  Study Chair,  UNC Lineberger Comprehensive Cancer Center   

Study ID Numbers:  CDR0000304498; CALGB-50201; NCT00062114
Record last reviewed:  July 2004
Last Updated:  April 5, 2005
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00062114
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08