Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Rituximab and Alemtuzumab in Treating Older Patients With Progressive Chronic Lymphocytic Leukemia

Basic Trial Information

Objectives

Primary

1. To compare the rate of complete and overall response in elderly patients with progressive chronic lymphocytic leukemia (CLL) treated with one of two doses of rituximab combined with alemtuzumab to determine if the use of modified-dose rituximab significantly affects outcome.

Secondary

1. To monitor and assess toxicity of these regimens.
2. To determine the overall and progression-free survival, time to clinical response, time to next treatment, and duration of response in patients treated with these regimens
3. To assess the correlation between risk stratification prognostic markers (i.e., CD38, ZAP-70, FISH, and IgVH mutation) and clinical outcome.
4. To assess response to these regimens using both the NCI-WG 96 criteria and an expanded definition of response for patients in complete remission, including immunohistochemical examination of the bone marrow and sensitive flow cytometry (4-6 color) of blood for minimal residual disease and CT scans for residual adenopathy.
5. To determine the mechanism of action of rituximab and alemtuzumab and to detail the in vivo effect of this regimen on critical aspects of the immune system in select patients with CLL.

Entry Criteria

Disease Characteristics:

• Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:
  • Minimum threshold peripheral lymphocyte count of 5 x 10⁹/L (CLL variant) OR palpable adenopathy > 1 cm or palpable splenomegaly (SLL variant)
  • Immunophenotypic demonstrations of a population of B-lymphocytes (as defined by CD19+) that are monoclonal (by light-chain exclusion) AND have ≥ 3 of the following characteristics:
    • CD5+
    • CD23+
    • Dim surface light chain expression
    • Dim surface CD20 expression
  • FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression (to exclude mantle cell lymphoma)

• Has progressive, symptomatic CLL, defined by at least one of the following:
  • Weight loss > 10% within the past 6 months attributable to progressive CLL (grade 2 or higher)
  • Extreme fatigue attributable to progressive CLL (grade 3 or higher)
  • Fevers > 100.5° F for 2 weeks without evidence of infection (grade 1 or higher)
  • Night sweats without evidence of infection (drenching)
  • Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10⁹/L
  • Rapidly progressive lymphadenopathy for which the largest node is ≤ 5 cm in any dimension
    • Largest lymph nodes involved in the neck, axilla, and groin need to be measured and followed for response

• No massive splenomegaly > 6 cm below left costal margin, at rest, on clinical examination

• No lymphadenopathy > 5 cm in any diameter

Prior/Concurrent Therapy:

• No prior treatment for CLL
• More than 4 weeks since prior major surgery
• No concurrent continuous systemic corticosteroids
  • Prior corticosteroids are allowed but not at time of pre-registration to the study

Patient Characteristics:

• ECOG performance status 0-3
• Creatinine ≤ 2 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 times ULN
• AST ≤ 3.0 times ULN (unless due to CLL involvement of the liver)
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after completion of study therapy
• None of the following comorbid conditions:
  • New York Heart Association class III or IV heart disease
  • Recent myocardial infarction (within the past month)
  • Uncontrolled infection
  • HIV/AIDS
  • Serological evidence of active hepatitis B infection (HBsAg or HBeAg positive)
  • Positive hepatitis C serology
• No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
• No other active primary malignancy requiring treatment or that limits survival to ≤ 2 years, except for in situ carcinoma of the cervix or breast or non-metastatic basal cell or squamous cell carcinoma of the skin

Expected Enrollment

Outcomes

Rate of complete and overall response

Toxicity as assessed by NCI CTC v4.0 criteria

Outline

This is a multicenter study. Patients are stratified according to FISH risk (low [13q14-] vs intermediate [12+, no abnormality, all other abnormalities] vs high [17p13-,11q22-]). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab IV on days 8, 15, 22, and 29 in course 1. In courses 2 and 3, patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive alemtuzumab as in arm I. Patients also receive low-dose rituximab IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in course 1 and on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in courses 2 and 3. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow samples are collected periodically for cytogenetic and biomarker analysis.

After completion of study therapy, patients are followed up periodically for 5 years.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Clive Zent, MD, Protocol chair		Ph: 507-266-1154

U.S.A.
Arizona
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Georgia
	Savannah
	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
		O. George Negrea, MD	Ph:  912-692-2000
Illinois
	Bloomington
	St. Joseph Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Bloomington%
	Illinois CancerCare - Bloomington
		John Kugler, MD	Ph:  309-243-3605
	Canton
	Graham Hospital
		John Kugler, MD	Ph:  309-243-3605
	Illinois CancerCare - Canton
		John Kugler, MD	Ph:  309-243-3605
	Carthage
	Illinois CancerCare - Carthage
		John Kugler, MD	Ph:  309-243-3605
	Memorial Hospital
		John Kugler, MD	Ph:  309-243-3605
	Chicago
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	Eureka
	Eureka Community Hospital
		John Kugler, MD	Ph:  309-243-3605
	Illinois CancerCare - Eureka
		John Kugler, MD	Ph:  309-243-3605
	Galesburg
	Galesburg Clinic, PC
		John Kugler, MD	Ph:  309-243-3605
	Illinois CancerCare - Galesburg
		John Kugler, MD	Ph:  309-243-3605
	Havana
	Illinois CancerCare - Havana
		John Kugler, MD	Ph:  309-243-3605
	Mason District Hospital
		John Kugler, MD	Ph:  309-243-3605
	Kewanee
	Illinois CancerCare - Kewanee Clinic
		John Kugler, MD	Ph:  309-243-3605
	Macomb
	Illinois CancerCare - Macomb
		John Kugler, MD	Ph:  309-243-3605
	McDonough District Hospital
		John Kugler, MD	Ph:  309-243-3605
	Monmouth
	Illinois CancerCare - Monmouth
		John Kugler, MD	Ph:  309-243-3605
	OSF Holy Family Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Normal
	BroMenn Regional Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Community Cancer Center
		John Kugler, MD	Ph:  309-243-3605
	Illinois CancerCare - Community Cancer Center
		John Kugler, MD	Ph:  309-243-3605
	Ottawa
	Community Hospital of Ottawa
		John Kugler, MD	Ph:  309-243-3605
	Oncology Hematology Associates of Central Illinois, PC - Ottawa
		John Kugler, MD	Ph:  309-243-3605
	Pekin
	Cancer Treatment Center at Pekin Hospital
		John Kugler, MD	Ph:  309-243-3605
	Illinois CancerCare - Pekin
		John Kugler, MD	Ph:  309-243-3605
	Peoria
	CCOP - Illinois Oncology Research Association
		John Kugler, MD	Ph:  309-243-3605
	Methodist Medical Center of Illinois
		Clinical Trials Office - Methodist Medical Center of Illinois	Ph:  309-243-3000
	Oncology Hematology Associates of Central Illinois, PC - Peoria
		John Kugler, MD	Ph:  309-243-3605
	OSF St. Francis Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Proctor Hospital
		John Kugler, MD	Ph:  309-243-3605
	Peru
	Illinois CancerCare - Peru
		John Kugler, MD	Ph:  309-243-3605
	Illinois Valley Community Hospital
		John Kugler, MD	Ph:  309-243-3605
	Princeton
	Illinois CancerCare - Princeton
		John Kugler, MD	Ph:  309-243-3605
	Perry Memorial Hospital
		John Kugler, MD	Ph:  309-243-3605
	Rockford
	Swedish-American Regional Cancer Center
		Clinical Trials Office - Swedish-American Regional Cancer Center	Ph:  815-489-4413
	Spring Valley
	Illinois CancerCare - Spring Valley
		John Kugler, MD	Ph:  309-243-3605
Indiana
	Beech Grove
	St. Francis Hospital and Health Centers - Beech Grove Campus
		Howard Gross, MD	Ph:  937-832-1093
	Richmond
	Reid Hospital & Health Care Services
		Howard Gross, MD	Ph:  937-832-1093
Iowa
	Ames
	McFarland Clinic, PC
		Clinical Trials Office - McFarland Clinic, PC	Ph:  515-239-2621
	Cedar Rapids
	Cedar Rapids Oncology Associates
		Clinical Trials Office - Cedar Rapids Oncology Associates	Ph:  319-363-2690
	Mercy Regional Cancer Center at Mercy Medical Center
		Deborah Wilbur	Ph:  319-398-6011
	Mason City
	Mercy Cancer Center at Mercy Medical Center - North Iowa
		Clinical Trials Office - Mercy Cancer Center at Mercy Medical Center - North Iowa	Ph:  641-422-6304
	Sioux City
	Mercy Medical Center - Sioux City
		Donald Wender, MD, PhD	Ph:  712-252-0088
	Siouxland Hematology-Oncology Associates, LLP
		Donald Wender, MD, PhD	Ph:  712-252-0088
	St. Luke's Regional Medical Center
		Donald Wender, MD, PhD	Ph:  712-252-0088
Michigan
	Marquette
	Upper Michigan Cancer Center at Marquette General Hospital
		Clinical Trials Office - Upper Michigan Cancer Center at Marquette General Hospital	Ph:  906-225-3467
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Missouri
	Bolivar
	Central Care Cancer Center at Carrie J. Babb Cancer Center
		Robert Carolla	Ph:  417-326-7200 800-592-5110
	Branson
	Skaggs Cancer Center at Skaggs Regional Medical Center
		Robert Carolla	Ph:  417-348-8032
	Cape Girardeau
	Southeast Cancer Center
		Alan Lyss, MD	Ph:  314-996-5514
	Jefferson City
	Goldschmidt Cancer Center
		Alan Lyss, MD	Ph:  314-996-5514
	Rolla
	Phelps County Regional Medical Center
		Robert Carolla	Ph:  573-458-8899
	Saint Louis
	Comprehensive Cancer Care, PC
		Alan Lyss, MD	Ph:  314-996-5514
	Missouri Baptist Cancer Center
		Alan Lyss, MD	Ph:  314-996-5514
	Springfield
	CCOP - Cancer Research for the Ozarks
		Robert Carolla	Ph:  417-269-4520
	Hulston Cancer Center at Cox Medical Center South
		Robert Carolla	Ph:  417-269-5257
Montana
	Billings
	Billings Clinic - Downtown
		Clinical Trials Office - Billings Clinic - Downtown	Ph:  800-996-2663
			Email: research@billingsclinic.org
	CCOP - Montana Cancer Consortium
		Benjamin Marchello, MD	Ph:  406-238-6290
	Hematology-Oncology Centers of the Northern Rockies - Billings
		Benjamin Marchello, MD	Ph:  406-238-6290
	St. Vincent Healthcare Cancer Care Services
		Benjamin Marchello, MD	Ph:  406-238-6290
	Bozeman
	Bozeman Deaconess Cancer Center
		Benjamin Marchello, MD	Ph:  406-238-6290
	Butte
	St. James Healthcare Cancer Care
		Benjamin Marchello, MD	Ph:  406-238-6290
	Great Falls
	Great Falls Clinic - Main Facility
		Benjamin Marchello, MD	Ph:  406-238-6290
	Sletten Cancer Institute at Benefis Healthcare
		Benjamin Marchello, MD	Ph:  406-238-6290
	Havre
	Northern Montana Hospital
		Benjamin Marchello, MD	Ph:  406-238-6290
	Helena
	St. Peter's Hospital
		Benjamin Marchello, MD	Ph:  406-238-6290
	Kalispell
	Glacier Oncology, PLLC
		Benjamin Marchello, MD	Ph:  406-238-6290
	Kalispell Medical Oncology at KRMC
		Benjamin Marchello, MD	Ph:  406-238-6290
	Kalispell Regional Medical Center
		Benjamin Marchello, MD	Ph:  406-238-6290
	Missoula
	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
		Clinical Trials Office - Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Ph:  406-329-7029
Nevada
	Las Vegas
	CCOP - Nevada Cancer Research Foundation
		John Ellerton, MD, CM	Ph:  702-384-0013
North Carolina
	Asheboro
	Randolph Hospital
		Clinical Trails Office - Randolph Hospital	Ph:  336-832-0821
	Goldsboro
	Wayne Memorial Hospital, Incorporated
		James Atkins, MD	Ph:  919-580-0000
	Greensboro
	Moses Cone Regional Cancer Center at Wesley Long Community Hospital
		Clinical Trials Office - Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Ph:  336-621-8374
	Hendersonville
	Pardee Memorial Hospital
		James Radford, MD	Ph:  828-692-8045
	Kinston
	Kinston Medical Specialists
		Contact Person	Ph:  252-559-2200 ext. 201
	Reidsville
	Annie Penn Cancer Center
		Clinical Trials Office - Annie Penn Cancer Center	Ph:  336-621-8374
	Statesville
	Iredell Memorial Hospital
		Ruby Grimm, MD	Ph:  704-873-2219
North Dakota
	Bismarck
	Bismarck Cancer Center
		Edward Wos, DO	Ph:  701-323-5741
	Medcenter One Hospital Cancer Care Center
		Edward Wos, DO	Ph:  701-323-5741
	Mid Dakota Clinic, PC
		Clinical Trials Office - Mid Dakota Clinic, PC	Ph:  701-530-6950
	St. Alexius Medical Center Cancer Center
		Clinical Trials Office - St. Alexius Medical Center Cancer Center	Ph:  701-530-6950
Ohio
	Canton
	Aultman Cancer Center at Aultman Hospital
		Clinical Trials Office - Aultman Cancer Center at Aultman Hospital	Ph:  330-363-6891
	Dayton
	CCOP - Dayton
		Howard Gross, MD	Ph:  937-832-1093
	David L. Rike Cancer Center at Miami Valley Hospital
		Clinical Trials Office - David L. Rike Cancer Center at Miami Valley Hospital	Ph:  937-208-2079
	Good Samaritan Hospital
		Howard Gross, MD	Ph:  937-832-1093
	Grandview Hospital
		Howard Gross, MD	Ph:  937-832-1093
	Samaritan North Cancer Care Center
		Howard Gross, MD	Ph:  937-832-1093
	Findlay
	Blanchard Valley Medical Associates
		Howard Gross, MD	Ph:  937-832-1093
	Franklin
	Middletown Regional Hospital
		Howard Gross, MD	Ph:  937-832-1093
	Greenville
	Wayne Hospital
		Howard Gross, MD	Ph:  937-832-1093
	Kettering
	Charles F. Kettering Memorial Hospital
		Clinical Trials Office - Charles F. Kettering Memorial Hospital	Ph:  937-298-3399 ext. 57556
	Lima
	St. Rita's Medical Center
		Clinical Trials Office - St. Rita's Medical Center	Ph:  419-226-9617
	Troy
	UVMC Cancer Care Center at Upper Valley Medical Center
		Clinical Trials Office - UVMC Cancer Care Center at Upper Valley Medical Center	Ph:  937-440-4842
Pennsylvania
	Hershey
	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
		Clinical Trials Office - Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Ph:  717-531-3779
			Email: CTO@hmc.psu.edu
	Lewistown
	Lewistown Hospital
		David Claxton	Ph:  717-242-7143
	Scranton
	Hematology and Oncology Associates of Northeastern Pennsylvania
		Martin Hyzinski, MD	Ph:  570-558-3020
	Mercy Hospital Cancer Center - Scranton
		Martin Hyzinski, MD	Ph:  570-558-3020
	State College
	Mount Nittany Medical Center
		David Claxton	Ph:  814-231-7000
Virginia
	Danville
	Danville Regional Medical Center
		Clinical Trials Office - Danville Regional Medical Center	Ph:  434-799-3753
Wisconsin
	Johnson Creek
	UW Cancer Center Johnson Creek
		Julie Chang	Ph:  920-699-3500
	La Crosse
	Gundersen Lutheran Center for Cancer and Blood
		Clinical Trials Office - Gundersen Lutheran Cancer Center	Ph:  608-775-2385
			Email: cancerctr@gundluth.org
	Madison
	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
		Clinical Trials Office - University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Ph:  608-262-5223
Wyoming
	Sheridan
	Welch Cancer Center at Sheridan Memorial Hospital
		Benjamin Marchello, MD	Ph:  406-238-6290

Registry Information
Official Title		A Phase II Randomized Trial Comparing Standard and Low Dose Rituximab: Initial Treatment of Progressive Chronic Lymphocytic Leukemia in Elderly Patients Using Alemtuzumab, and Rituximab
Trial Start Date		2010-10-08
Trial Completion Date		2012-02-01 (estimated)
Registered in ClinicalTrials.gov		NCT01013961
Date Submitted to PDQ		2009-11-06
Information Last Verified		2012-02-11
NCI Grant/Contract Number		CA21115

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