Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Waldenstrom's Macroglobulinemia

Lymphoma Clinical Trial

Official title:

Phase II Pilot Study Of Rituximab Plus CHOP In Patients With Newly Diagnosed Waldenstrom's Macroglobulinemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00060346
• Other study ID #: CDR0000301634
• Secondary ID: U10CA021115E1A02
• Status: Terminated
• Phase: Phase 2
• Start date: October 5, 2004
• Est. completion date: August 2012

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 locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab 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 newly diagnosed Waldenstrom's macroglobulinemia.

Description:

OBJECTIVES:

• Determine the response rate of patients with newly diagnosed Waldenstrom's macroglobulinemia treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.

• Determine the associated toxic effects of this regimen, specifically the frequency of febrile neutropenia, in these patients.

• Determine the progression-free survival of patients treated with this regimen.

• Correlate baseline cytogenetic features and gene expression profiles with response in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Patients receive rituximab intravenously (IV) over approximately 4 hours, cyclophosphamide IV over 5-30 minutes, doxorubicin IV over 5-15 minutes, and vincristine IV over 1 minute on day

1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

ACTUAL ACCRUAL: A total of 16 patients were accrued for this study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: August 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

• Diagnosis of Waldenstrom's macroglobulinemia confirmed by the presence of the following:

• Bone marrow lymphoplasmacytosis with: > 10% lymphoplasmacytic cells OR aggregates or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic cells on the bone marrow biopsy (measured within 4 weeks prior to registration)

• Measurable disease defined as a quantitative immunoglobulin M (IgM) monoclonal protein of > 1,000 mg/dL obtained within 4 weeks prior to registration

• Cluster of differentiation 20 (CD20) positive stain of bone marrow or lymph node samples obtained < 8 weeks prior to registration

• Impaired bone marrow function due to infiltration by lymphoplasmacytic lymphoma, defined by 1 of the following:

• Hemoglobin no greater than 11 g/dL

• Serum viscosity level relative to water of at least 4.0 centipoise

• Absolute neutrophil count at least 1,000/mm^3

• Platelet count at least 75,000/mm^3

• Bilirubin no greater than 3.0 mg/dL

• Aspartate aminotransferase (AST) no greater than 3 times upper limit of normal

• Creatinine no greater than 3.0 mg/dL

• Age of 18 and over

• ECOG (Eastern Cooperative Oncology Group) performance status 0-1

• Must be symptomatic with 1 of the following:

• Clinically significant anemia (hemoglobin no greater than 11 g/dL)

• Bulky lymphadenopathy

• Symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding, or retinal hemorrhage)

• History of heart disease allowed only if 1 of the following is demonstrated by echocardiography, multigated acquisition scan (MUGA), exercise MUGA, or coronary catheterization:

• Ejection fraction of at least 45%

• Normal fractional shortening of the left ventricle

• Must have been tested for hepatitis B surface antigen within 2 weeks of registration

• Negative pregnancy test

• Fertile patients must use effective contraception

EXCLUSION CRITERIA:

• Prior treatment for Waldenstrom's macroglobulinemia

• Prior anti-CD20 therapy

• Concurrent steroids exceeding 10 mg prednisone (or equivalent) per day

• Prior irradiation if less than 4 weeks had elapsed prior to registration and the date of last treatment

• Prior anthracyclines

• Prior malignancy except curatively treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer curatively treated with surgery alone and from which patient has been disease free for at least 5 years

• Active heart disease

• Pregnant or nursing

• Myocardial infarction within the past 3 months

• Congestive heart failure

• Symptomatic ventricular arrhythmia

Related Conditions & MeSH terms

• Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Biological:
• rituximab
Rituximab is given intravenously. The initial rate is 50 mg/hr for the 1st hour. If no toxicity, the rate may be escalated in 50 mg/hr increments at 30-minute intervals to a maximum of 400 mg/hr. If the first dose is well tolerated, the initial rate for subsequent dose is 100 mg/hr, increased in 100 mg/hr increments at 30-minute intervals, not to exceed 400 mg/hr. If the patient experiences fever and rigors, the antibody infusion is discontinued. The severity of the side effects should be evaluated. If the symptoms improve, the infusion is continued initially at half the previous rate. Following the antibody infusion, the intravenous line should be maintained for medications as needed. If there are no complications after one hour of observation, the intravenous line may be discontinued.

Drug:
• cyclophosphamide
Cyclophosphamide will be given at a dosage of 750 mg/m² intravenously on day 1 of each cycle (1 cycle =21 days) for 6 cycles. Dose is based on surface area calculated based on actual body weight. The drug should be administered as a rapid IV infusion over 5 to 30 minutes.
• Doxorubicin
Doxorubicin will be given intravenously at a dosage of 50 mg/m² on day 1 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight. Doxorubicin should be administered as a continuous infusion into tubing of a freely flowing intravenous line for 5 -15 minutes. Avoid extravasation.
• Prednisone
Prednisone will be administered at 100 mg/m² orally, days 1-5 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight.
• Vincristine
Vincristine will be administered 1.4 mg/m² intravenously (Maximum dose = 2.0 mg) on day 1 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight. Given as IV push over 1 minute, using extravasation precautions.

Locations

Country	Name	City	State
United States	McFarland Clinic, PC	Ames	Iowa
United States	AnMed Cancer Center	Anderson	South Carolina
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	Billings Clinic - Downtown	Billings	Montana
United States	Billings Clinic Cancer Center	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Our Lady of Mercy Medical Center Comprehensive Cancer Center	Bronx	New York
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Genesis Medical Center - West Campus	Davenport	Iowa
United States	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center	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	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Metro Health Hospital	Grand Rapids	Michigan
United States	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan
United States	Great Falls Clinic	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Holland Community Hospital	Holland	Michigan
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	William N. Wishard Memorial Hospital	Indianapolis	Indiana
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	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	Beebe Medical Center	Lewes	Delaware
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Southwest Medical Center	Liberal	Kansas
United States	St. Rita's Medical Center	Lima	Ohio
United States	Meeker County Memorial Hospital	Litchfield	Minnesota
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Hackley Hospital	Muskegon	Michigan
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Reid Hospital & Health Care Services, Incorporated	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Interlakes Oncology/Hematology PC	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
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	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Cotton-O'Neil Cancer Center	Topeka	Kansas
United States	St. Francis Comprehensive Cancer Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Medical Oncology and Hematology Associates - West Des Moines	West Des Moines	Iowa
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Wilson Medical Center	Wilson	North Carolina
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Cleveland Clinic - Wooster	Wooster	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (1)

Abonour R, Zhang LA, Rajkumar V, et al.: Phase II pilot study of rituximab + CHOP in patients with newly diagnosed Waldenstroms macroglobulinemia, an Eastren Cooperative Oncology Group trial (study E1A02). [Abstract] Blood 110 (11): A-3616, 2007.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response to Treatment	Objective response assessed using standard myeloma response criteria. Objective response is defined as a > 50% reduction in the quantitative IgM or M-Spike levels from baseline levels. Response must be documented by two measurements separated by at least 3 weeks.	Every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry