Clinical trial NCT00062114: Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Non-Hodgkin's Lymphoma
Official title: A Phase II Study To Evaluate The Safety And Efficacy Of Zevalin (IND # BB IND 4850) Therapeutic Regimen In Patients With Transformed CD20 + B-Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult immunoblastic large cell lymphoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-06-06
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: This phase II trial is studying how well giving yttrium Y 90 ibritumomab tiuxetan together with rituximab works in treating patients with progressive non-Hodgkin's lymphoma.

Detailed description: 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 1 (or 2 if needed) imaging scan between days 2-5. 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.

Eligibility 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

Primary outcomes:
measure: Overall response rate
timeFrame: Up to 4 years
measure: Duration of response
timeFrame: Up to 4 years
Secondary outcomes:
measure: Complete response (CR), unconfirmed CR, and partial response
timeFrame: Up to 4 years
measure: Event-free survival
timeFrame: Up to 4 years
measure: Time to progression
timeFrame: Up to 4 years
measure: Time to next lymphoma treatment
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Medical Office -Vandever Medical Office
state: California
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
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: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services, Incorporated
state: Indiana
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Topeka
country: United States
facility: Cotton-O'Neil Cancer Center
state: Kansas
city: Topeka
country: United States
facility: St. Francis Comprehensive Cancer Center
state: Kansas
city: Lewiston
country: United States
facility: Central Maine Comprehensive Cancer Center at Central Maine Medical Center
state: Maine
city: Elkton MD
country: United States
facility: Union Hospital Cancer Program at Union Hospital
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Brigham and Women's Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: Kalamazooaa
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: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology at KRMC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Keene
country: United States
facility: Kingsbury Center for Cancer Care at Cheshire Medical Center
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center
state: New Hampshire
city: Rochester
country: United States
facility: Frisbie Memorial Hospital
state: New Hampshire
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center Comprehensive Cancer Center
state: New York
city: Glens Falls
country: United States
facility: Charles R. Wood Cancer Center at Glens Falls Hospital
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Wilson
country: United States
facility: Wilson Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's Cancer Network at St. Luke's Hospital
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Sioux Valley Hospital and University of South Dakota Medical Center
state: South Dakota
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Latter Day Saints Hospital
state: Utah
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Thomas C. Shea, MD
role: STUDY_CHAIR
References: