Chronic Lymphocytic Leukemia Clinical Trial

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

Summary

RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Giving rituximab together with alemtuzumab may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying two different doses of rituximab to compare how well they work when given together with alemtuzumab in treating older patients with progressive leukemia-cll/" >chronic lymphocytic leukemia.

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Full Description

OBJECTIVES:

Primary

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

To monitor and assess toxicity of these regimens.
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
To assess the correlation between risk stratification prognostic markers (i.e., CD38, ZAP-70, fluorescent in situ hybridization (FISH), and IgVH mutation) and clinical outcome.
To assess response to these regimens using both the 1996 National Cancer Institute Working Group (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 computed tomography (CT) scans for residual adenopathy.
To determine the mechanism of action of rituximab and alemtuzumab and to determine mechanisms of resistance of a subpopulation of CLL cells to these drugs.

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 A: 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 intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), 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 cycles.
Arm B: Patients receive alemtuzumab as in arm A. Patients also receive low-dose rituximab IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 and on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in cycless 2 and 3. Treatment repeats every 28 days for up to 3 cycles.

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

Alemtuzumab dose for Cycle 1 Week 1 of both Arms A and B requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1).

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

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:

Minimum threshold peripheral lymphocyte count of 5 x 10^9/L (CLL variant) OR palpable adenopathy > 1 cm or palpable splenomegaly 9small lymphocytic lymphoma [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 immunoglobulin heavy chain/cyclin D1 gene (IGH/CCND1) and/or immunostaining is negative for cyclin D1 expression (to exclude mantle cell lymphoma)

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 10^9/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

Exclusion Criteria:

Prior treatment for CLL
Massive splenomegaly > 6 cm below left costal margin, at rest, on clinical examination
Lymphadenopathy > 5 cm in any diameter
New York Heart Association class III or IV heart disease
Recent myocardial infarction (within the past month)
Uncontrolled infection
Infection with the human immunodeficiency virus (HIV/AIDS)
Serological evidence of active hepatitis B infection (HBsAg or HBeAg positive)
Positive hepatitis C serology
Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
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
Major surgery within 4 weeks prior to pre-registration

Concomitant use of continuous systemic corticosteroids

Prior corticosteroids are allowed but not at time of pre-registration to the study

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 2

Estimated Enrollment:

31

Study ID:

NCT01013961

Recruitment Status:

Terminated

Sponsor:

ECOG-ACRIN Cancer Research Group

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There are 87 Locations for this study

See Locations Near You

Mayo Clinic Scottsdale
Scottsdale Arizona, 85259, United States
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
Fort Lauderdale Florida, 33308, United States
Ella Milbank Foshay Cancer Center at Jupiter Medical Center
Jupiter Florida, 33458, United States
CCOP - Mount Sinai Medical Center
Miami Beach Florida, 33140, United States
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
Savannah Georgia, 31405, United States
Rush-Copley Cancer Care Center
Aurora Illinois, 60504, United States
Illinois CancerCare - Bloomington
Bloomington Illinois, 61701, United States
St. Joseph Medical Center
Bloomington Illinois, 61701, United States
Graham Hospital
Canton Illinois, 61520, United States
Illinois CancerCare - Canton
Canton Illinois, 61520, United States
Illinois CancerCare - Carthage
Carthage Illinois, 62321, United States
Memorial Hospital
Carthage Illinois, 62321, United States
University of Chicago Cancer Research Center
Chicago Illinois, 60637, United States
Eureka Community Hospital
Eureka Illinois, 61530, United States
Illinois CancerCare - Eureka
Eureka Illinois, 61530, United States
Galesburg Clinic, PC
Galesburg Illinois, 61401, United States
Illinois CancerCare - Havana
Havana Illinois, 62644, United States
Illinois CancerCare - Kewanee Clinic
Kewanee Illinois, 61443, United States
Illinois CancerCare - Macomb
Macomb Illinois, 61455, United States
McDonough District Hospital
Macomb Illinois, 61455, United States
Illinois CancerCare - Monmouth
Monmouth Illinois, 61462, United States
OSF Holy Family Medical Center
Monmouth Illinois, 61462, United States
BroMenn Regional Medical Center
Normal Illinois, 61761, United States
Community Cancer Center
Normal Illinois, 61761, United States
Illinois CancerCare - Community Cancer Center
Normal Illinois, 61761, United States
Community Hospital of Ottawa
Ottawa Illinois, 61350, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
Ottawa Illinois, 61350, United States
Cancer Treatment Center at Pekin Hospital
Pekin Illinois, 61554, United States
Illinois CancerCare - Pekin
Pekin Illinois, 61603, United States
Proctor Hospital
Peoria Illinois, 61614, United States
CCOP - Illinois Oncology Research Association
Peoria Illinois, 61615, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria Illinois, 61615, United States
Methodist Medical Center of Illinois
Peoria Illinois, 61636, United States
OSF St. Francis Medical Center
Peoria Illinois, 61637, United States
Illinois CancerCare - Peru
Peru Illinois, 61354, United States
Illinois Valley Community Hospital
Peru Illinois, 61354, United States
Illinois CancerCare - Princeton
Princeton Illinois, 61356, United States
Swedish-American Regional Cancer Center
Rockford Illinois, 61104, United States
Illinois CancerCare - Spring Valley
Spring Valley Illinois, 61362, United States
CCOP - Carle Cancer Center
Urbana Illinois, 61801, United States
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove Indiana, 46107, United States
Reid Hospital & Health Care Services
Richmond Indiana, 47374, United States
McFarland Clinic, PC
Ames Iowa, 50010, United States
Cedar Rapids Oncology Associates
Cedar Rapids Iowa, 52403, United States
Mercy Regional Cancer Center at Mercy Medical Center
Cedar Rapids Iowa, 52403, United States
Mercy Cancer Center at Mercy Medical Center - North Iowa
Mason City Iowa, 50401, United States
Siouxland Hematology-Oncology Associates, LLP
Sioux City Iowa, 51101, United States
Mercy Medical Center - Sioux City
Sioux City Iowa, 51102, United States
St. Luke's Regional Medical Center
Sioux City Iowa, 51104, United States
Tulane Cancer Center Office of Clinical Research
Alexandria Louisiana, 71315, United States
Hematology-Oncology Clinic
Baton Rouge Louisiana, 70809, United States
Feist-Weiller Cancer Center at Louisiana State University Health Sciences
Shreveport Louisiana, 71130, United States
Borgess Medical Center
Kalamazoo Michigan, 49001, United States
West Michigan Cancer Center
Kalamazoo Michigan, 49007, United States
Bronson Methodist Hospital
Kalamazoo Michigan, 49007, United States
Upper Michigan Cancer Center at Marquette General Hospital
Marquette Michigan, 49855, United States
Mayo Clinic Cancer Center
Rochester Minnesota, 55905, United States
Central Care Cancer Center at Carrie J. Babb Cancer Center
Bolivar Missouri, 65613, United States
Skaggs Cancer Center at Skaggs Regional Medical Center
Branson Missouri, 65616, United States
Southeast Cancer Center
Cape Girardeau Missouri, 63703, United States
Goldschmidt Cancer Center
Jefferson City Missouri, 65109, United States
Mercy Clinic Cancer and Hematology - Rolla
Rolla Missouri, 65401, United States
Phelps County Regional Medical Center
Rolla Missouri, 65401, United States
Missouri Baptist Cancer Center
Saint Louis Missouri, 63131, United States
CCOP - Cancer Research for the Ozarks
Springfield Missouri, 65802, United States
St. John's Regional Health Center
Springfield Missouri, 65804, United States
Hulston Cancer Center at Cox Medical Center South
Springfield Missouri, 65807, United States
CCOP - Nevada Cancer Research Foundation
Las Vegas Nevada, 89106, United States
Randolph Hospital
Asheboro North Carolina, 27203, United States
Wayne Memorial Hospital, Incorporated
Goldsboro North Carolina, 27534, United States
Moses Cone Regional Cancer Center at Wesley Long Community Hospital
Greensboro North Carolina, 27403, United States
Pardee Memorial Hospital
Hendersonville North Carolina, 28791, United States
Kinston Medical Specialists
Kinston North Carolina, 28501, United States
Annie Penn Cancer Center
Reidsville North Carolina, 27320, United States
Iredell Memorial Hospital
Statesville North Carolina, 28677, United States
Medcenter One Hospital Cancer Care Center
Bismarck North Dakota, 58501, United States
Mid Dakota Clinic, PC
Bismarck North Dakota, 58501, United States
St. Alexius Medical Center Cancer Center
Bismarck North Dakota, 58502, United States
Aultman Cancer Center at Aultman Hospital
Canton Ohio, 44710, United States
Grandview Hospital
Dayton Ohio, 45405, United States
Good Samaritan Hospital
Dayton Ohio, 45406, United States
David L. Rike Cancer Center at Miami Valley Hospital
Dayton Ohio, 45409, United States
Samaritan North Cancer Care Center
Dayton Ohio, 45415, United States
CCOP - Dayton
Dayton Ohio, 45420, United States
Blanchard Valley Medical Associates
Findlay Ohio, 45840, United States
Middletown Regional Hospital
Franklin Ohio, 45005, United States
Wayne Hospital
Greenville Ohio, 45331, United States
Charles F. Kettering Memorial Hospital
Kettering Ohio, 45429, United States
St. Rita's Medical Center
Lima Ohio, 45801, United States
UVMC Cancer Care Center at Upper Valley Medical Center
Troy Ohio, 45373, United States
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia Ohio, 45385, United States
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey Pennsylvania, 17033, United States
Lewistown Hospital
Lewistown Pennsylvania, 17044, United States
Mercy Hospital Cancer Center - Scranton
Scranton Pennsylvania, 18501, United States
Hematology and Oncology Associates of Northeastern Pennsylvania
Scranton Pennsylvania, 18510, United States
Mount Nittany Medical Center
State College Pennsylvania, 16803, United States
U.T. Medical Center Cancer Institute
Knoxville Tennessee, 37920, United States
Danville Regional Medical Center
Danville Virginia, 24541, United States
UW Cancer Center Johnson Creek
Johnson Creek Wisconsin, 53038, United States
Gundersen Lutheran Center for Cancer and Blood
La Crosse Wisconsin, 54601, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison Wisconsin, 53792, United States
Riverview UW Cancer Center at Riverview Hospital
Wisconsin Rapids Wisconsin, 54494, United States

How clear is this clinincal trial information?

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 2

Estimated Enrollment:

31

Study ID:

NCT01013961

Recruitment Status:

Terminated

Sponsor:


ECOG-ACRIN Cancer Research Group

How clear is this clinincal trial information?

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