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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00060346
Recruitment Status : Terminated (slow accrual)
First Posted : May 7, 2003
Results First Posted : February 12, 2013
Last Update Posted : February 13, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Brief 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.


Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: cyclophosphamide Drug: Doxorubicin Drug: Prednisone Drug: Vincristine Phase 2

Detailed 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Pilot Study Of Rituximab Plus CHOP In Patients With Newly Diagnosed Waldenstrom's Macroglobulinemia
Study Start Date : June 2004
Actual Primary Completion Date : December 2011
Actual Study Completion Date : August 2012


Arm Intervention/treatment
Experimental: Rituximab + CHOP

Rituximab 375 mg/m2 day 1 of a 21-day cycle, followed by:

Cyclophosphamide 750 mg/m2 Doxorubicin 50 mg/m2 Vincristine 1.4 mg/m2 and Prednisone 100 mg/m2 daily

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.
Other Names:
  • IDEC-C2B8
  • Chimeric anti-CD20 monoclonal antibody
  • Rituxan
  • NSC# 687451

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.

Other Names:
  • Cytoxan
  • CTX
  • CPM
  • Neosar

Drug: 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.

Other Names:
  • Adriamycin
  • Rubex
  • Adriamycin RDF
  • Adriamycin PFS
  • hydroxydaunorubicin
  • ADR

Drug: 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.
Other Names:
  • Deltasone
  • Orasone
  • Medicortone
  • Panasol-S
  • Liqui-Pred

Drug: 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.

Other Names:
  • Vinsacar PFS
  • vincristine sulfate
  • VCR
  • leucocristine
  • LCR




Primary Outcome Measures :
  1. Objective Response to Treatment [ Time Frame: 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 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00060346


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Locations
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United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, Delaware
Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Illinois
Rush-Copley Cancer Care Center
Aurora, Illinois, United States, 60507
Joliet Oncology-Hematology Associates, Limited - West
Joliet, Illinois, United States, 60435
Carle Cancer Center at Carle Foundation Hospital
Urbana, Illinois, United States, 61801
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Elkhart General Hospital
Elkhart, Indiana, United States, 46515
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
William N. Wishard Memorial Hospital
Indianapolis, Indiana, United States, 46202
Howard Community Hospital
Kokomo, Indiana, United States, 46904
Center for Cancer Therapy at LaPorte Hospital and Health Services
La Porte, Indiana, United States, 46350
Saint Anthony Memorial Health Centers
Michigan City, Indiana, United States, 46360
Reid Hospital & Health Care Services, Incorporated
Richmond, Indiana, United States, 47374
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
Memorial Hospital of South Bend
South Bend, Indiana, United States, 46601
Saint Joseph Regional Medical Center
South Bend, Indiana, United States, 46617
United States, Iowa
McFarland Clinic, PC
Ames, Iowa, United States, 50010
Genesis Regional Cancer Center at Genesis Medical Center
Davenport, Iowa, United States, 52803
Genesis Medical Center - West Campus
Davenport, Iowa, United States, 52804
Mercy Capitol Hospital
Des Moines, Iowa, United States, 50307
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
Des Moines, Iowa, United States, 50309
Medical Oncology and Hematology Associates at Mercy Cancer Center
Des Moines, Iowa, United States, 50314
Mercy Cancer Center at Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
John Stoddard Cancer Center
Des Moines, Iowa, United States, 50316-2301
Mercy Cancer Center at Mercy Medical Center - North Iowa
Mason City, Iowa, United States, 50401
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, United States, 51101
Mercy Medical Center - Sioux City
Sioux City, Iowa, United States, 51104
St. Luke's Regional Medical Center
Sioux City, Iowa, United States, 51104
Medical Oncology and Hematology Associates - West Des Moines
West Des Moines, Iowa, United States, 50266
United States, Kansas
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, United States, 67042
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States, 67068
Southwest Medical Center
Liberal, Kansas, United States, 67901
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States, 67124
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States, 67042
Tammy Walker Cancer Center at Salina Regional Health Center
Salina, Kansas, United States, 67401
Cotton-O'Neil Cancer Center
Topeka, Kansas, United States, 66604
St. Francis Comprehensive Cancer Center
Topeka, Kansas, United States, 66606
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States, 67152
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67203
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
CCOP - Wichita
Wichita, Kansas, United States, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States, 67156
United States, Maryland
Union Hospital Cancer Program at Union Hospital
Elkton MD, Maryland, United States, 21921
United States, Michigan
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, United States, 49017
Mecosta County Medical Center
Big Rapids, Michigan, United States, 49307
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
Lacks Cancer Center at Saint Mary's Health Care
Grand Rapids, Michigan, United States, 49503
Spectrum Health Hospital - Butterworth Campus
Grand Rapids, Michigan, United States, 49503
Metro Health Hospital
Grand Rapids, Michigan, United States, 49506
Holland Community Hospital
Holland, Michigan, United States, 49423
Borgess Medical Center
Kalamazooaa, Michigan, United States, 49001
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
Hackley Hospital
Muskegon, Michigan, United States, 49442
Lakeland Regional Cancer Care Center - St. Joseph
St. Joseph, Michigan, United States, 49085
Munson Medical Center
Traverse City, Michigan, United States, 49684
United States, Minnesota
MeritCare Bemidji
Bemidji, Minnesota, United States, 56601
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States, 55432
Hutchinson Area Health Care
Hutchinson, Minnesota, United States, 55350
Meeker County Memorial Hospital
Lichfield, Minnesota, United States, 55355
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, United States, 55109
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, United States, 55109
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55415
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, United States, 55422-2900
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, United States, 55379
HealthEast Cancer Care at St. Joseph's Hospital
St Paul, Minnesota, United States, 55102
Park Nicollet Cancer Center
St. Louis Park, Minnesota, United States, 55416
Regions Hospital Cancer Care Center
St. Paul, Minnesota, United States, 55101
United Hospital
St. Paul, Minnesota, United States, 55102
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
HealthEast Cancer Care at Woodwinds Health Campus
Woodbury, Minnesota, United States, 55125
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States, 55125
United States, Missouri
Saint Louis University Cancer Center
Saint Louis, Missouri, United States, 63110
United States, Montana
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States, 59101
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
St. Vincent Healthcare Cancer Care Services
Billings, Montana, United States, 59101
Billings Clinic Cancer Center
Billings, Montana, United States, 59107-5100
Billings Clinic - Downtown
Billings, Montana, United States, 59107-7000
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
St. James Healthcare Cancer Care
Butte, Montana, United States, 59701
Great Falls Clinic - Main Facility
Great Falls, Montana, United States, 59405
Great Falls Clinic
Great Falls, Montana, United States, 59405
St. Peter's Hospital
Helena, Montana, United States, 59601
Glacier Oncology, PLLC
Kalispell, Montana, United States, 59901
Kalispell Medical Oncology at KRMC
Kalispell, Montana, United States, 59901
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Community Medical Center
Missoula, Montana, United States, 59801
Guardian Oncology and Center for Wellness
Missoula, Montana, United States, 59804
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States, 59807-7877
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States, 59807
United States, New Jersey
Hunterdon Regional Cancer Center at Hunterdon Medical Center
Flemington, New Jersey, United States, 08822
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
Marlton, New Jersey, United States, 08053
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
Fox Chase Virtua Health Cancer Program at Virtua West Jersey
Voorhees, New Jersey, United States, 08043
United States, New York
Our Lady of Mercy Medical Center Comprehensive Cancer Center
Bronx, New York, United States, 10466
Interlakes Oncology/Hematology PC
Rochester, New York, United States, 14623
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Wayne Radiation Oncology
Goldsboro, North Carolina, United States, 27534
Rutherford Hospital
Rutherfordton, North Carolina, United States, 28139
Wilson Medical Center
Wilson, North Carolina, United States, 27893-3428
United States, North Dakota
CCOP - MeritCare Hospital
Fargo, North Dakota, United States, 58122
MeritCare Broadway
Fargo, North Dakota, United States, 58122
United States, Ohio
Aultman Cancer Center at Aultman Hospital
Canton, Ohio, United States, 44710-1799
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Grandview Hospital
Dayton, Ohio, United States, 45405
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Samaritan North Cancer Care Center
Dayton, Ohio, United States, 45415
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428
CCOP - Dayton
Dayton, Ohio, United States, 45429
Community Oncology Group at Cleveland Clinic Cancer Center
Independence, Ohio, United States, 44131
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
St. Rita's Medical Center
Lima, Ohio, United States, 45801
Middletown Regional Hospital
Middletown, Ohio, United States, 45044
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
Cleveland Clinic - Wooster
Wooster, Ohio, United States, 44691
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-0001
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Lewistown Hospital
Lewistown, Pennsylvania, United States, 17044
Geisinger Medical Group - Scenery Park
State College, Pennsylvania, United States, 16801
Mount Nittany Medical Center
State College, Pennsylvania, United States, 16803
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, United States, 18711
United States, South Carolina
AnMed Cancer Center
Anderson, South Carolina, United States, 29621
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, South Dakota
Avera Cancer Institute
Sioux Falls, South Dakota, United States, 57105
Medical X-Ray Center, PC
Sioux Falls, South Dakota, United States, 57105
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
Wilford Hall Medical Center
Lackland AFB, Texas, United States, 78236
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
United States, Wisconsin
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States, 54601
United States, Wyoming
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
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Study Chair: Rafat Abonour, MD Indiana University Melvin and Bren Simon Cancer Center

Publications of Results:
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.

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Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00060346     History of Changes
Other Study ID Numbers: CDR0000301634
U10CA021115 ( U.S. NIH Grant/Contract )
E1A02 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
First Posted: May 7, 2003    Key Record Dates
Results First Posted: February 12, 2013
Last Update Posted: February 13, 2013
Last Verified: February 2013
Keywords provided by Eastern Cooperative Oncology Group:
Waldenstrom macroglobulinemia
Rituximab
CHOP
Additional relevant MeSH terms:
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Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Liposomal doxorubicin
Vincristine
Antibodies
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents