Clinical trial NCT00005609: Rituximab in Treating Patients With Waldenstrom's Macroglobulinemia
Official title: Rituximab for Waldenstrom's Macroglobulinemia (WM): A Phase II Pilot Study for Untreated or Previously Treated Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: Waldenström macroglobulinemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-02-16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of rituximab in treating patients who have Waldenstrom's macroglobulinemia.

Detailed description: OBJECTIVES: I. Determine the response rate in previously treated and previously untreated patients with Waldenstrom's macroglobulinemia receiving rituximab. II. Determine the associated toxicities with this treatment, specifically the frequency of febrile or hypotensive events, in this patient population.

OUTLINE: Patients are stratified according to prior treatment (yes vs no). Patients with prior treatment are further stratified according to type of treatment (alkylating agents vs purine nucleoside analogues). Patients receive rituximab IV over 4 hours on days 1, 8, 15, and 22. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 66 patients (33 per stratum) will be accrued for this study within 36 months.

Eligibility criteria: DISEASE CHARACTERISTICS: Waldenstrom's macroglobulinemia confirmed by the following: Bone marrow lymphoplasmacytosis with: Greater than 10% lymphoplasmacytic cells OR Aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy AND Measurable disease defined as quantitative IgM monoclonal protein greater than 1,000 mg/dL Bone marrow lymphoplasmacytosis and beta-2 microglobulin in the serum are not considered measurable Impaired bone marrow function due to infiltration by lymphoplasmacytic lymphoma Hemoglobin less than 11 g/dL OR Serum viscosity level relative to water greater than 4.0 Symptomatic with clinically significant anemia (less than 11 g/dL), bulky lymphadenopathy that is symptomatic, or symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding, retinal hemorrhage)

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-3 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: SGOT less than 3 times upper limit of normal Bilirubin less than 2.0 mg/dL Renal: Creatinine no greater than 3.0 mg/dL Cardiovascular: No myocardial infarction within past 6 months No significant arrhythmia within past 3 months Hypertension allowed provided controlled with medication Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Concurrent reversible complications (e.g., hyperuricemia, hyperviscosity) allowed provided therapy for complication initiated and complications subsiding Other prior malignancies allowed provided curatively treated and currently disease free

PRIOR CONCURRENT THERAPY: No more than 2 prior regimens allowed Prior tandem transplant considered 2 prior regimens Chemotherapy prior to bone marrow transplantation as part of induction considered 1 prior regimen Retreatment with same regimen (e.g., repeated alkylating agents) considered 1 prior regimen Biologic therapy: No prior anti-CD20 therapy At least 1 month since prior epoetin alfa No concurrent epoetin alfa for 2 months after registration Chemotherapy: At least 28 days since prior alkylating agents At least 28 days since prior purine nucleoside analogues Endocrine therapy: At least 28 days since prior corticosteroid therapy Radiotherapy: At least 4 weeks since prior radiotherapy Surgery: Not specified Other: Concurrent digoxin to control atrial fibrillation allowed

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Duarte
country: United States
facility: Cancer Center and Beckman Research Institute, City of Hope
state: California
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center - Palo Alto
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Inc.
state: Colorado
city: Wilmington
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: Veterans Affairs Medical Center - Gainsville
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Decatur
country: United States
facility: Veterans Affairs Medical Center - Atlanta (Decatur)
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at The University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Albany
country: United States
facility: Veterans Affairs Medical Center - Albany
state: New York
city: Bronx
country: United States
facility: Albert Einstein Comprehensive Cancer Center
state: New York
city: Bronx
country: United States
facility: MBCCOP-Our Lady of Mercy Cancer Center
state: New York
city: Brooklyn
country: United States
facility: Veterans Affairs Medical Center - Brooklyn
state: New York
city: New York
country: United States
facility: Veterans Affairs Medical Center - New York
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Veterans Affairs Medical Center - Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital Oncology Program
state: Ohio
city: Tulsa
country: United States
facility: CCOP - Sooner State
state: Oklahoma
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Veterans Affairs Medical Center - Pittsburgh
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Madison
country: United States
facility: Veterans Affairs Medical Center - Madison
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: MBCCOP - San Juan
city: San Juan
country: Puerto Rico
facility: Veterans Affairs Medical Center - San Juan
city: Pretoria
country: South Africa
facility: Pretoria Academic Hospitals
Study officials:
affiliation: Mayo Clinic
name: Morie A. Gertz, MD
role: STUDY_CHAIR
References:
citation: Gertz MA, Abonour R, Heffner LT, Greipp PR, Uno H, Rajkumar SV. Clinical value of minor responses after 4 doses of rituximab in Waldenstrom macroglobulinaemia: a follow-up of the Eastern Cooperative Oncology Group E3A98 trial. Br J Haematol. 2009 Dec;147(5):677-80. doi: 10.1111/j.1365-2141.2009.07892.x. Epub 2009 Sep 14.
citation: Gertz MA, Rue M, Blood E, Kaminer LS, Vesole DH, Greipp PR. Multicenter phase 2 trial of rituximab for Waldenstrom macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98). Leuk Lymphoma. 2004 Oct;45(10):2047-55. doi: 10.1080/10428190410001714043.
citation: Ghobrial IM, Fonseca R, Greipp PR, Blood E, Rue M, Vesole DH, Gertz MA; Eastern Cooperative Oncology Group. Initial immunoglobulin M 'flare' after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia: an Eastern Cooperative Oncology Group Study. Cancer. 2004 Dec 1;101(11):2593-8. doi: 10.1002/cncr.20658.